HEMATOONCOLOGY

antibodies develop.
APPROACH TO TRANSFUSION 3. TTI –Transfusion transmitted infections
REACTION
• Bacterial contamination – Platelets: RDP > SDP
• Any transfusion reaction, any grade, severity → → gram positive bacteria
transfusion should be stopped. – PRBC: → gram negative rods
• MCC Post transfusion hepatitis – HBV
4. TRALI – Transfusion related acute lung injury
• Onset within < 6hrsQ
• Allo antibodies of donor attack WBCs of
recipient → attacked WBCs get clogged in
pulmonary capillaries → cytokines released →
Exudate release → ARDS like picture
• MCC of transfusion related death.
TRALI TACO
• SOB, Crepitations - • SOB, crepitations – B/L,
1. AHTR - Acute hemolytic transfusion reaction B/L, diffuse diffuse
• It is d/t ABO mismatch • B/L lung infilterate on • B/L lung infilterate on
Xray Xray.
• Symptoms -
• It is d/t non • It is d/t cardiogenic
– In conscious patient - burning pain along the cardiogenic pulmonary pulmonary edema
vein/iv line edema • It is d/t volume overload
– In comatose patients - bleeding & oozing • Symptoms - fever • Risk factor - h/o
from puncture sites d/t DIC because it is a immune overload state like CKD,
– Fever reaction HF
– ↓BP/↑HR – ↓BP/↑HR • Symptoms - no fever
– AKI -↑ S.Creatinine /flank pain – Normal JVP – Normal BP/↑HR
– Intravascular hemolysis - ↑LDH/↓S. – Normal BNP – ↑JVP
Haptoglobin /hemoglobinuria • Treatment – no – ↑BNP
– DCT /DAT +ve response to diuretics Treatment - diuretics
2. FNHTR - Febrile non hemolytic transfusion 5. Minor Allergic reaction
reactionQ
• Causes urticaria & itching.
• No signs of hemolysis
• Symptoms - fever/chills. • Stop the transfusion for 10-15 mins and resume
once urticaria settles down.
• Cause - WBCs of donor reacting with allo
antibodies of recipient. • Tx: antihistamine
• Treatment - analgesic 6. Anaphylaxis
• Prevention – leukodepletion filter Q
• Causes: urticarial, wheeze/SOB, stridor and ↓BP.
• More regular the transfusion, more the allo
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• Tx: antihistamine /dexamethasone/ epinephrine • C/F: thrombocytopenia, bruises, superficial

(1mg in 1:1000 I.M.) bleeding, petechiae
• If recurrent anaphylactic reactions occur, • Tx: IV Ig (urgent Tx), corticosteroids show
always r/o IgA deficiency. affect after 1-2 weeks.

DELAYED REACTION • HPA1a Antigen is also responsible for

FNAIT (fetal & neonatal allo immune
1. DHTR – delayed hemolytic transfusion reaction
thrombocytopenia)
• Similar to AHTR, but less severe
3. TA-GVHD
• ↓Hb, Intravascular hemolysis → ↑LDH/↓
S.Haptoglobin /hemoglobinuria • In recent bone marrow transplant/ SCID,
the recipient will not have any sort of immune
• DCT /DAT +ve
system to mount a immune response against
• It occurs d/t minor antigens → Duffy Ag, donor T cells → donor T cells attack recipient’s
KIDDO Ag‘s anamnestic response stem cells in bone marrow & results in profound
• Tx: supportive BM suppression.
2. PTP – post transfusion purpura • Prevention: with irradiated blood products.
• Causes: Antibodies against platelet antigen
HPA1a Ag in the subsequent transfusions. INTEGRATED APPROACH TO ANEMIA
• Presents with delayed thrombocytopenia after
(↓HB)
5-7 days of transfusion.

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• Drugs like antibiotics – ceftriaxone/piperacillin/ – Ferric carboxymaltose( FCM)

cefotetan can induce warm type HA. – Ferrumoxitol

I. Microcytic – Isomaltosidase - max. concentration of iron

1. IDA • IV iron is safe in renal diseases & pregnancy.

• MCC of iron deficiency • Reticulocyte index <2

• Cause - blood loss • Response to iron supplementation –

• C/F - subjective features → fatigue, pica, – Earliest - subjective improvement (within 12-
koilonychia, platynychia, angular cheilitis 24hrs)

• Plummer Vinson syndrome - IDA + esophageal – Fatigue will improve, pica will improve.

webs + dysphagia: premalignant condition - – Koilonychia will take 3- 6 months to improve

↑risk of squamous cell cancer – Hematological change – BM → erythroid
• Dx: earliest - ↓S. Ferritin Q hyperplasia (48hrs)

• Transferrin saturation = Fe/TIBC <18 – On P/S - ↑reticulocyte Hb on smear →

reticulocytosis
• S. transferrin /log ferritin >2
2. AOCD - Anemia of chronic diseases
• Hepcidin ↓↓
• Any inflammation can result in ACOD.
• Mentzer index = MCV/RBC >13
• S.Ferritin ↑
• Gold standard for dx: BM Aspiration. Stained
• Transferrin saturation = Fe/ TIBC >18%
using Prussian blue.
• S. transferrin /log Ferritin < 2
• TOC: Iron supplementation – oral or IV
• TOC: erythropoietin
• Indications for IV iron - pregnancy /intolerance
• Reticulocyte index < 2
to oral iron
3. Β- thalassemia minor
• Oral iron - 1st choice → MC S/E of oral iron →
GI S/E • Incidental finding, Asymptomatic

• Mildly ↓Hb, ↓ MCV

• Formulations - Fe gluconate (lowest iron content)
/Fe SO4 / Fe fumarate (highest content of iron) • Mentzer index = MCV/RBC <13

• IV iron formulation - • Normal Fe indices

– IV iron gluconate • NESTROFT can be used as screening test for

– LMW Dextran thalassemia in areas of high prevalence.

– Iron sucrose • Hb electrophoresis - HbA2 (α2δ2 ) >3.5%Q

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Β thalassemia Α- thalassemia
• Never present at fetal life or birth • Can present at birth
• Take 6- 12 months to manifest • Classification
• Classification - – 1α - asymptomatic/ normal smear
– Thalassemia major – – 2α-
ƒ Symptomatic + transfusion dependent. ƒ Asymptomatic
ƒ Need regular transfusion → iron ƒ Mild ↓Hb + microcytosis (Hb electrophoresis is normal)
overload therefore iron chelators used – 3α-
- IV deferoxamine / p/o deferiprone / ƒ α thalassemia intermedia
p/o deferasirox
ƒ Symptomatic at birth itself
ƒ Target Hb >10g/dl (ensure adequate
ƒ Severe microcytosis
growth in children)
ƒ Moderate – severe anemia (7- 9gm/dl), splenomegaly
ƒ Reticulocyte index <2
ƒ β4 tetramers - HbH disease, can be detected in Hb
– Thalassemia intermedia –
electrophoresis, smear seen as golf ball.
ƒ Symptomatic but not transfusion
– 4α-
dependent.
ƒ Behave as thalassemia major in utero.
ƒ Reticulocyte < 2
ƒ ϒ4 tetramer formation in fetal life itself, a/k/a Hb Barts.
– Thalassemia minor -
ƒ Can be detected in Hb electrophoresis.
ƒ Asymptomatic + mild ↓ Hb +
ƒ Death in uterus without intrauterine transfusion.
microcytosis Reticulocyte index >2
ƒ Reason of death - severe anemia → cardiac collapse →
hydrops

4. Sideroblastic anemia II. Normocytic Anemia

• Iron cannot be utilized due to defective Extravascular hemolysis Intavascular hemolysis
porphyrin synthesis. • Destruction of RBCs in • Destruction of RBCs in
• ↑S.Ferritin, ↑Transferrin saturation (Fe/TIBC) spleen blood vessel, rouleax
>50- 60%, reticulocyte index <2 • Jaundice formation /agglutination
• BM aspiration – ringed sideroblasts (RBC • On P/S - spherocytes • Hemoglobinuria
precursors with iron accumulation in the form Cold HA results in
• Warm HA results in •
of mitochondria) are seen.Q
extravascular hemolysis intravascular hemolysis
• 2 conditions where ringed Sideroblastic are Avoid cold exposure
• Tx: corticosteroids •
seen -
treat main causes
– Sideroblastic anemia + Splenectomy in
• Rituximab helpful
– Refractory anemia with ringed sideroblasts refractory in waldenstrom
(MDS) macroglobulinemia
• Causes: DCT –ve: Non immune mediated HA
– Hereditary causes – ALA synthase defect
– Pyridoxine deficiency – dietary /isoniazid/
chronic alcohol/lead poisoning
• Tx: Pyridoxine
– Chelators like succimer /dimercaprol.

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1. Thrombotic microangiopathy • Patient has h/o exposure to causes →

present with ↓Hb, ↑LDH , Hemoglobinuria,
• Triad – MAHA + thrombocytopenia + End organ ↓S.Haptoglobin (intravascular hemolysis)
damage (Renal /CNS)
• P/S - Heinz bodies (seen only in vital stains like
2. PNH new methylene blue)

• Acquired PIG-A gene defect in stem cell – Blister/Bite cells (seen in routine stains like
wright giemsa stain)
• PIG-A defect → ↓GPI anchors → ↓CD55
(DAF)/CD59 (MIRL) expressionQ • Tx - supportive treatment

• Triad - Nocturnal hemoglobinuria + Pancytopenia 4. Hereditary spherocytosis

with classic cellular marrow + Thrombosis (MCC
• MC defect – Ankyrin defectQ
of death)
• Family h/o anemia / h/o gallstones/ jaundice /
• Infections – 2nd MCC of death d/t pancytopenia
cholecystectomy
• IOC - flow cytometry (FLAER)Q • Patient presents with anemia + P/S →
• TOC - allogenic stem cell transplantation spherocytes (DCT –ve)

• 1st line of Tx - Eculizumab (Anti C5 Mab) / • Spherocytes also seen in warm type AIHA, r/o
Ravulizumab (Anti C5 Mab)Q with DCT.

– S/E - ↑risk of fulminant meningococcal • Extravascular hemolysis (spleen) - jaundice

infection / ↑risk of pigmented gallstones / chronic leg
ulcers /splenomegaly
– ↓ intravascular hemolysis
• Screening - OFT → ↑ fragility of spherocytes
– No effect on extravascular hemolysis / ↑MCHC

3. G6PD deficiency • AGLT (Acidified glycerol lysis test) - ↑sensitivity

• Mc enzyme deficiency in the world • IOC - Flowcytometry (EMA binding)Q

• TOC - splenectomy
• ↓NADPH → ↓glutathione in RBC → ↑risk of
damage by oxidative stress – Indications - transfusion dependent
• Causes – drugs: → Primaquine, ciprofloxacin,
sulfonamides, uricase, IV methylene blue,
doxorubicin, nitrofurantoin /DKA/ infections /
Diet → fava beans

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5. Sickle cell disease - • Tx -

• Single point mutation that changes CAG – Transfusions

sequence that code for glutamate at β6 position ƒ Exchange transfusion –
to CTG sequence that codes for valine at β6
position. ○ Indication: acute chest syndrome
&acute stroke
• Clinical features -
○ Goal: to keep HbS <30%
– Anemia (P/S → Drepanocytes, normal MCV)
ƒ Simple transfusion –
– Vaso-occlusion – pain, Dactylitis
○ Indication: splenic sequestration
• More common in children, a/k/a hand foot
syndrome ○ Goal: Hb = 9-10gm%
– Sequestration crisis - – Drugs like crizanlizumab - anti P selectin
monoclonal antibody
ƒ Acute chest syndrome - pneumonia -
like presentation, present with B/L ƒ Voxelotor – inhibit HbS polymerizationQ
crepitations, infilterates in CXR, SOB, → • Reticulocytic Index <2 %
TOC - exchange transfusion + antibiotics
• Aplastic anemia
ƒ Splenic sequestration – present with
sudden anemia & massive splenomegaly, – P/S - Pancytopenia
seen in 2-3yrs of age. Older children have – BM aspiration – hypocellularity (↑↑fat)
autosplenectomy d/t repeated splenic
infarcts by 4-5yrs of age → ↑risk of – Classified into –
infections ƒ Inherited form – Fanconi anemia
ƒ Organism associated with osteomyelitis in ○ Young patients, manifest as BM ↓,
sickle cell disease patients is Salmonella. present as aplastic anemia
– Others –
○ Numerous skeletal malformations
ƒ Stroke – incidentally diagnosed
○ ↑risk of cancer
ƒ Priapism – teens/young
○ Screening Ix - DEB (Diepoxybutane) /
ƒ Pulmonary hypertension MMC (Mitomycin C test) tests
ƒ Chronic leg ulcers ○ Confirmatory test – genetic testing
ƒ Renal papillary necrosis – hematuria, ƒ Acquired form - 1° & 2°
↓urine osmolarity
○ 1° – young adults , present with
• IOC - Hb electrophoresisQ
aplastic anemia, TOC - Allogenic
– HbSS – 75-95% HbS, <2% HbF, 0% HbA SCT (best match – matched sibling
– HbAS (sickle cell trait) - donor): 1st line therapy – triple therapy
→ immunosuppressive drugs like
ƒ Asymptomatic normally
Horse ATG + calcineurin inhibitors
ƒ In pregnancy/major surgery/ high altitude like Tacrolimus/ Cyclosporine +
→ renal papillary necrosis Eltrombopag
○ Mc symptom - hematuria ○ 2° – MC is drugs – chemotherapy (dose
ƒ 40% HbS, 60% HbA, no sickle cell in smear dependent) /antibiotics/antithyroid
drugs /colchicine idio-syncratic

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III. Macrocytic Anemia

Megaloblastic anemia

Bald tongue d/t atrophy of papilla, seen in IDA, B12

def. anemia (beefy red tongue)

B12 deficiency
• Neurological changes – Axonal peripheral
neuropathy, SACD, psychiatric changes &
dementia
• Neurological changes precede anemia
• Occurs in vegans
• Patients can have ↑MMA (methyl malonyl acid),
↑HomocysteineQ
• Knuckle hyperpigmentation
Koilonychia - IDA
Folate deficiency
• No neurological manifestations
• Occurs in animal meat eaters mainly (green
leafy vegetable deficiency)Q

Myelodysplastic syndrome (MDS)

• ↑risk of AML – Old age + pancytopenias (MC-
macrocytic anemia)
• P/S - dysplastic cells +/- blasts.
• BM aspiration – cellular marrow + dysplastic
cells +/- blasts Knuckle hyperpigme ntation - B12 deficiency
• Tx – allogenic stem cell transplantation (if fit +
high risk patient)
– Hypomethylating agents (unfit /low risk
patient) inhibit DNA methyl transferase
(DNMT)
– Eg - Azacitidine & Decitabine
– Lenalidomide – TOC for isolated 5q deletion : Bite cells Blister cells
females with thrombocytosis
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G6PD deficiency

• Basophilic stippling retained Sickle cell disease- drepanocytes in P/SQ

RNA fragments in RBCs seen in
• Cabot rings d/t retention of ineffective INTEGRATED APPROACH TO
arginine rich mitotic spindle erythropoiesisQ THROMBOCYTOPENIA
– Coarse basophilic stippling - lead poisoning &
Sideroblastic anemia
– Fine basophilic stippling – megaloblastic
anemia (B12 def./FA def.)

Thrombocytopenia – Clumped pseudo thrombocytopenia

Ringed sideroblasts seen in sideroblastic anemia, MDS

of refractory anemia with ringed sideroblasts

Golf ball inclusion seen in HbH disease (3α gene deletion)

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1. 2° ITP • Causes
• Causes – – Gold salts/ Procainamide / Sulfonamides/
Vancomycin /Heparin
– Autoimmune conditions ,Eg- SLE /APS
– Heparin induced thrombocytopenia (HIT)-
– Infections – HIV/ HCV
ƒ 2 types - Type 1 & Type 2 HIT
2. DITP

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Type 1 HIT Type 2 HIT

• Non immune mediated • Most important , associated with thrombosis , a/k/a HITTS
• Timing – occurs in 1st 2-3 days itself • Immune mediatedQ
• Symptoms – thrombocytopenia (platelet count >1 lakh • Timing of thrombocytopenia - D5-D10 (if patient is not exposed to
with ↓ <50%) Heparin in last 3 months), if patient is exposed to Heparin in last 3
months, then reaction can occur in 1st 24hrs itselfQ
• Risk - UFH > LMWH
• Symptoms – moderate thrombocytopenia (platelet count < 1 lakh with ↓
by >50%) & venous thromboembolic manifestations.
• Diagnosis –
– IOC - HIT Ab (antibody directed against platelet factor 4-Heparin complex)
4T Scoring system-
– 0-3 score - low probability
HIT Ab testing done only in
– 4-5 score - intermediate probability
intermediate & high risk
– 6-8 score - high clinical probability
4T scoring parameters-
– Degree/severity of thrombocytopenia
– Timing of events
– Thrombosis
– Other causes
Titres of HIT Ab –
– If ≥ 1.5 optical density – HIT
– If 0.6- 1.4 optical density – confirm HIT on basis of SRA & HIPA
– If <0.6 optical density – r/o HIT
• Treatment-
– Stop all form of Heparin lifelong /Warfarin
– Start alternative anticoagulant, continue for 1-2 months, if any evidence for thrombosis then continue or
3-6months.
– Alternative anticoagulant of choice – Argatroban /Fondaparinux / Danaparaoid /DOAC
– Warfarin can be started once platelet count >1.5.

3. 1° ITP – Late Tx (>3 months)- Rituximab (anti

CD 20Mab) , splenectomy (done only in
• Diagnosis of exclusion refractory cases)
• No splenomegaly – Newer drugs -
• Clinical features - young /middle aged females ƒ Thrombopoietin receptor agonist, Eg-
• P/S - isolated thrombocytopenia +/- giant Eltrombopag, Avatrombopag
platelets +/- Immature platelet fraction >6-7% ƒ TPO mimetic- Romoplostim
• BM aspiration – normal megakaryopoiesis ƒ Fostamanitib (SYK inhibitor – spleen
• Treatment - early tx & late tx tyrosine kinase inhibitor)
– Early Tx (<3months) – cortisocosteroids + ƒ Rilzabrutinib (BTK inhibitor – bruton
IVIG +/- Platelet concentrate & Tranexamic tyrosine kinase inhibitor)
acid if patient bleeding

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Thrombotic microangiopathy (TMA) • 1° TMA – HUS/TTP

• 2° TMA-
– Drug (calcineurin inhibitor like cyclosporine,
tacrolimus/ antiplatelet drugs like
Ticlopidine, Clopidogrel/ Bevacizumab)
– HELLP syndrome /SRC (scleroderma renal
crisis) / malignant HTN

HUS TTP
• Cause - endothelial injury • Cause - Platelet trapping (ADAMST13 defect) → large
• Can be due to Shiga toxin (EHEC, O157:H7 or O104: VWF multimers are going to persist in circulation →
H4) or complement dysregulation VWF & platelets occlude in microvasculature
Shiga toxin - • Can be congenital (1/3rd cases, a/k/a Upshaw schulman
– Children <5yrs, bloody diarrhea disease) or acquired (mc, 2/3rd of cases are d/t
– a/k/a classical HUS D+ or typical HUS antibodies)

– Triad - MAHA + ↓platelet (less severe) + AKI (more • TTP is common in 3rd trimester pregnancy.
severe) • Triad – MAHA + ↓Platelets (more severe) +
– Treatment – conservative treatment Neurological (seizure/altered mental status)

No antibiotics. Platelets transfusions are C/I. • +/- fever +/- AKI (less severe ) → Pentad

• Complement dysregulation – here defect is in • IOC – ADAMST13 testingQ

alternate complement pathway • TOC- Plasma exchange
– Eg - Loss of function mutation of CFH /CFI /CD-46 • Newer drug – Caplacizumab (anti VWF Mab)
→ loss of inhibition of alternate complement pathway
→ endothelial injury
Or
Gain of function → mutation of C3/CFB → overactivation
of endothelial complement pathway → endothelial injury
– a/k/a HUS D -ve /atypical HUS
– Not associated with bloody diarrhea
– TOC- Eculizumab +/- Plasma exchange

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OTHER BLEEDING DISORDERS

vWD Other hereditary bleeding disorders
• Mc inherited bleeding disorder, >85% Q
• Bernard Soulier syndrome –
• Function of VWF- – AR , defective GpIb-IXQ
– Carry factor 8 & stabilize it so that t1/2 of – ↓Platelet adhesion
factor 8 ↑ – P/S - thrombocytopenia & giant platelets
– It acts as platelet glue, binds to platelet – Ix - flow cytometry / ↓ RIPA
GpIb – IX receptor on one side & • Glanzmann thrombasthenia -
subendothelial collagen on other side,
– AR, defect in GpIIb/IIIaQ
increasing platelet adhesion.
• 3 types of VWD - – ↓platelet aggregation
– Type 1 - AD, MC, >85% cases → partial – P/S - normal platelet count /no giant platelets
quantitative defect
– Ix - normal RIPA/ defective aggregation to all other
– Type 2 - qualitative defect.
agonist ADP, Collagen , Epinephrine.
ƒ 2A (AD), 2B(AD), 2M (AD), 2N (AR)
• Gray platelet syndrome –
– Type 3- AR, complete quantitative defect
– Defect in NBEAL2 gene defect
• Type 2 & Type 3 can present like Hemophilias
• Clinical features- – Absent α granules
– Bleeding – Dental/ ENT – P/S - giant platelets & thrombocytopenia
• Ix-
– Myelofibrosis, splenomegaly
– CBC- normal platelet in all types except 2B.
– In E/M, absent α granules
– PT/INR – normal
• Hermansky pudlak syndrome
– aPTT- mild ↑( mild ↓ in Factor VIII)
– Multiple genes implicated
– ↓ RIPA or ↓R:Co assay except Type 2B
(RIPA ↑) – P/S - normal, normal platelet count & no giant platelets

– Type 2N – everything normal except factor – C/F - pulmonary fibrosis , oculo-cutaneous albinism
VIII levels (↓↓) – On Electron microscopy - absent δ granules
• Tx- – Platelet aggregation – absent 2° wave with ADP (1° wave is
– Type 1 VWD - DDAVP - ↑release of VWF intact)
from endothelial cells • Chediak-Higashi syndrome
– Defect in LYST geneQ
– Triad – defective neutrophils function with neutropenia {P/S
- giant azurophillic granules} + oculo-cutaneous albinism +
peripheral neuropathy + defective granular release
– P/S - normal platelet count, no giant platelets

COAGULATION DISORDERS ƒ d/t intron 22 inversion

• Mc inherited coagulation disorder is Hemophilia – Hemophilia B - Factor IX deficiency / ~20%
cases
• Types of hemophilias-
– Hemophilia C - Factor XI deficiency
– Hemophilia A
ƒ Factor VIII deficiencyQ
ƒ mc / ~80% cases
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– In Minor bleeds like Hemarthroses /minor

surgery, maintain factor levels at 40-50%
ƒ Factor VIII dose - 25units/kg
ƒ Factor IX dose – 50units/kg
– Newer drugs – Emicizumab (Bispecific
antibody) approved for Hemophilia AQ

Hemarthroses, mc joint involved is knee joint

ƒ Clotting factor inhibitor : Antibody against

factor VIII – TOC is recombinant Factor
VII A >FEIBA (activated Prothrombin
Hemophilic arthopathy – destruction of knee jointQ complex)

Clinical features Factor XI deficiency- AR

• Patient can have limb spanning ecchymosis • ↑↑↑aPTT (correct with mixing )
• Delayed bleeding is characteristic of like • Clinical features- present as slow oozing from
Hemophilias. mucous membrane after ENT/GU procedures
• Intramuscular hematomas • Tx – FFP

Ix Factor XII deficiency

• ↑↑aPTTt (correct with mixing)
• CBC- normal platelet count
• No bleeding
• PT/INR- normal
• aPTT- ↑↑↑ : corrects with mixing Factor XIII deficiency
↓ Factor VIII/ IX levels • aPTT normal
• Delayed bleeding (clot stability poor here)
• Tx: recombinant factor concentrate VIII/IX.
• Eg - delayed umbilical cord stump bleeding
• Dose - • Gold standard Ix - Factor XIII assay
– In acute bleeds (major ICH /major surgery), • Ix - clot lysis test
maintain factor levels at 80-100 %
– Mix clot with 5m urea → if clot dissolves
ƒ Factor VIII dose- 50 units /kg within next 24hrs
ƒ Factor IX- 100 units/kg – MCA test

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Overview Of Acute Leukemias

AML ALL
• Elderly, 60-70yrs • Children
• Leukostasis (d/t very high WBC count ,these WBCs can • Can present as lymphoma also
plug the capillaries of vital organs) • Present with lymphadenopathy → mc lymph node
– CNS- altered mental status, seizure involved is mediastinal → can cause SVC syndrome &
hepatosplenomegaly
– Pulmonary – SOB /Pulmonary infiltration /B/L
• Bony/lumbar pain
crepitations
• Tumor lysis syndrome
– Visual – blurring of vision d/t plugging of retinal
• CNS & testicles symptoms might arise once blasts
arteriole
are cleared in periphery.
– TOC of leukostasis – induction Chemotherapy
• All patients have to undergo LP & intrathecal
↓ If delayed chemotherapy is must.
• Flow cytometry – Pre B-ALL & Pre T-ALL
Tx - hydroxyurea /leukapheresis
– Precursor identification → CD34 /TdT+
• DIC → APL (AML-M3)Q
• Chloroma → granulocytic sarcomas – B-Cell → CD19+

– Can occur in skin (leukemia cutis)/ brain/bones/ oral – T-Cell → CD3+

cavity (gingival infiltration /gingival hyperplasia) ƒ Most of the T-cell tumors will have NOTCH
– Risk factors - mutation
• Child:
ƒ Young
– t(12;21) & ETV6/RUNX1Q
ƒ t(8;21)
– Favorable prognosis
ƒ M4/M5 (monocytoid variants)
– Hyperdiploidy (blasts have >50 chromosome)
• Diagnosis –
• Infant:
– Blasts ≥ 20% (peripheral blood /BM)
– T(4;11) – AFF1-MLL gene
– Exception –
– Unfavorable prognosis
ƒ Core binding leukemias-
– Hypodiploidy
→ t(8;21) AML-M2 → RUNX1-RUNX1T1 gene
Poor prognostic markers-
→ t(16;16) inv 16-AML-M4E0 → CBFB-MYH11 gene
• Philadelphia + ,t(9;22) BCR-ABL
ƒ APL - t(15;17) →PML-Rara fusionQ
• t(4;11) –AFF1-MLL gene
ƒ Excellent prognosis
Poor prognostic markers- • t(1;19)- TCF3-PBX1 gene

• Philadelphia +ve – t(9;22) → BCR-ABL • Hypodiploidy (<44 chromosome in blasts)

• t(6;9) → DEK-NUP214 gene • Complex karyotypic abnormality

• t(3;3) inv 3 →GATA-MECOM • ETP (early T-cell phenotype)/ MRD (minimal residual
disease after chemotherapy)
• MDS like – loss of chr 5/7/17 OR deletion of parts of
chr like 5q /7q deletion • Boys , infants ( <1yr)

• Complex karyotype - ≥ 3 changes • Adults

• Molecular changes - FLT3 mutation + NPM-1 wild type • B-Cell ALL in adults & T-Cell ALL in adults
mutation → poor prognosis

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Independent prognostic markers- • Tx: - V D P A regimen

• Age >60/70 yrs – V- Vincristine
• If ECOG ≥ 3
– D- Daunorubicin
• Treatment related acute AML –
– P- Prednisolone
– H/o of prior exposure to alkylating agents /radiation therapy /
– A- Peglycated Asparaginase
DNA topoisomerase II inhibitors.
+ intrathecal chemotherapy Ara-C &
– 5q/7q deletion (MDS like changes) is seen after 5-7yrs of
Methotrexate
exposure to alkylating agents/ radiation therapy And >2-3 yrs
– Newer drugs –
after exposure to DNA topoisomerase II inhibitors.
ƒ Blinatumomab (CD19 bispecific T-Cell
– MLL (new name – KMT2A) – t(9;11), located on 11q23
engager)
• Flow cytometry
ƒ Inotuzumab ozogamicin (anti CD22
– Myelod- CD13/33 (CD117/MPO )
IHC- MPO+ve, Mab)
– Precursor- CD34
– Monocytoid- CD11b (CD14/15/ 64) SBB+ve ,

– Erythroid – CD71 / CD 235A NSE+ve

– Megakaryoid – CD41/CD61 (monocytoid FAB

M4/M5)
PAS+ve

(Granular +erythroid/megakaryoid M6/M7)

– Auer rods - AML faggot cellsQ

• Tx: APL (acute promyelocytic leukemia) - ATRA + Arsenic trioxide
– 25% of cases who are treated with ATRA develop differentiation
syndrome
– Differentiation Syndrome –
ƒ C/F - SOB/ Hypoxemia/pulmonary infiltrate and crepitations
+ altered mental status + hypotension + AKI
ƒ TOC - Dexamethasone
• Tx: Non –APL –
– If fit (ECOG status < 3/ younger patient) for chemo : 7+3 +/-
Midostaurin
ƒ D1-D7 → Cytosine Arabinoside
ƒ D1-D3 → Daunorubicin
ƒ D8-D21 → Midostaurin, best for FLT3 mutations
– If unfit for chemo: Hypomethylating agents (Azacitidine/
Decitabine) + venetoclax (Bcl2 inhibitor or BH3 mimetic)
– Hypomethylating agents are not used in IDH mutations.
ƒ IDH1 Mutation – Ivosidenib
ƒ IDH 2 Mutation – Enasidenib
ƒ Sonic hedgehog inhibitor – Glasdegib
– Newer drug – Gemtuzumab ozogamicin: MOA - Gemtuzumab is
anti CD33 Mab & delivers toxic drug ozogamicin after binding.

* For Making Notes

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Cerebellum Quick Revision Notes

Down syndrome & ALL – BM aspiration – BM fibrosis

• Mc leukemia in down syndrome – ALL (risk is 10 • Any cancer associated with down syndrome-
- 20% times more in down syndrome) high treatment related mortality

• Occurs in <10yrs HODGKIN LYMPHOMA

• B-cell type of ALL • Young patients
• CRLF-2 Overexpression /JAK2 mutations • Present with painless lymphadenopathy,
supradiaphragmatic lymph nodes, MC – cervical
Down syndrome & AML lymphadenopathy, contiguous spread, extranodal
disease at time of presentation rare
• Acute megakaryotic Leukemia (AML M7) –most
• Alcohol intake ↑ pain in lymph nodes
specific in down syndromeQ
• B-symptoms - pel ebstein fever /night sweats,
• Neonatal – significant weight loss, 10-15% patients may
– GATA 1 mutation have pruritis
• NHL - infradiaphragmatic lymph nodes
– Transient myeloproliferative disorder involvement, extranodal disease common, non
– Asymptomatic + circulating blasts contiguous spread
(megakaryotic lineage) • Spleen is considered as nodal disease in HL &
as extranodal in NHL
20%
– Extranodal sites include Thymus, LN,
Develop Acute megakaryocytic leukemia (AMKL) in
Waldeyer’s ring
<4yrs age
cHL NLPHL
• 95% cases • 5% cases
• Variable prognosis • Excellent prognosis
• EBV association ~ 50% • Rare
• Histological subtypes • Variant RS cell /popcorn cells/ Lympho-histiocytic RS
– Nodular sclerosis type - mc ,females, in Bx- Collagen Cells
bands seen , lacunar RS Cell seen • CD15/30 -, CD20+
– Mixed cellularity – EBV association 50-70% , • Tx: R-CHOP + ISRT +/- Active surveillance
males>female, classic RS cell seen – Alternative regimen – ABVD
– Lymphocyte rich type - better prognosis among all – R - Rituximab (s/e-reactivation of hep B virus)
cHL, EBV association 30-50%, mononuclear RS cell – C - Cyclophosphamide (s/e – gonadal toxicity/ BM
seen suppression)
– Lymphocyte poor type – worst prognosis, associated – H - Hydroxydaunorubicin (s/e- cardiotoxicity)
with HIV, mummified type RS cell seen – O - Oncovin (s/e- peripheral neuropathy)
• RS cells – CD15/30+ CD20-
– P - Prednisone (s/e- bone toxicity)
• Tx: A B V D +/- Involved site Radiotherapy (ISRT )
– A -Adriamycin/ doxorubicin(s/e- cardiotoxicity)Q
– B -Bleomycin
– V -Vinblastine
– D -Dacarbazine ( s/e – gonadal toxicity/ BM
suppression / 2nd cancer- MDS & AML)
ƒ Brentuximab vedotin (anti CD30 Mab )
ƒ Pembrolizumab – immune check inhibitor

* For Making Notes

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Medicine

• Prognostic marker- IPS scoring

– Age >45yrs
– Male
– Hb <10.5g/dl
– S.albumin <4g/dl
– Stage IV disease/disseminated
– WBCs count (≥ 15,000)
– Absolute lymphocyte count < 600/μl
– DC lymphocyte <8%

Classic RS CellQ
Popcorn RS Cell

• Diagnosis of any lymphoma- LN Excision Bx >> Trucut Biopsy >>FNAC

• Staging & follow-up – FDG- PET

An Arbor Staging

* For Making Notes

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Cerebellum Quick Revision Notes

Aggressive B-Cell NHLs

NHL Presentation Clues Possible 1st line Rx
BL • Endemic BL present with jaw • HPE - medium cells , starry sky • Regime
• Most aggressive mass in children, 100% association appearance • R-CODOX-M /
with EBV • Ki67 >95%Q R-IVAC
• Sporadic BL present with • Marker- CD10+ • Intrathecal
Right iliac mass, variable EBV • Cytogenetic – CMYC overexpression – chemotherapy
associationQ 100% cases d/t ↑risk of CNS
• HIV Associated BL • t(8;14) – mcQ dissemination
lymphadenopathyQ
• t(2;8)
• t(8;22)
DLBCL Can present as nodal (LAN) / • HPE - large cells Regime- R-CHOP
• mc B-cell NHLQ Extranodal (mc site- GIT) • No starry sky appQ
• mc aggressive • Ki67 <95%
B-cell NHL • Marker –
• double hit/ triple – GCB →CD10/Bcl-6
hit DLBCL (worst
– ABC/non GCB (relatively poor
prognosis) - CMYC
prognosis)→CD10-/MUM1+
overexpression
• Cytogenetic changes-
+/- Bcl2 +/- Bcl 6
• Regime - – CMYC/MLL
EPOCH-R • No specific cytogenetic marker

MCL • Lymphadenopathy + GIT • CD5 +/CD23 - /CD10- Variable

involvement • HPE- small – medium cells
• Presents with polyposis • Cytogenetic –
– t(11;14) - cyclin D1
– Cyclin D1 –ve MCL-SOX 11
overexpression
MZL 1. Nodal MZL → lymphadenopathy • No specific immunophenotypic marker Variable, Eg- If H.pylori
2. Extranodal MZL → MALT • Diagnosis of exclusion - eradication therapy
lymphoma (depends on site). • Cytogenetic –
Infections associated – – mc- trisomy 8
– H.pylori – gastric maltoma – t(11;18) – MALT1 gene
– C.psittaci- orbital malt overexpression
lymphoma – t(14;18) - MALT1 gene
– Borrelia- cutaneous malt
lymphoma
– C.jejuni- S.I malt lymphoma
– Sjogren syndrome – ass. with
Parotid malt lymphomas &
gastric lymphomas
3. SMZL → splenomegaly +/- LAN,
associated with HCV → villous
lymphocytes in P/S (Hair like
projection seen in pole)

* For Making Notes

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Medicine

NHL Presentation Clues Possible 1st line Rx

FL • Mc indolent B-cell lymphoma • HPE – complete destruction of lymph • Treatment is based
• Present with painless peripheral node, follicles seen on grade.
lymphadenopathy • CD10+ • Not high grade- R
• Centrocytic tumor • Cytogenetic – t(14;18)- Bcl 2 only therapy
• Centroblast no. tells the grade of overexpressionQ • Semi-aggressive
the tumor. grade- R2 (Rituximab
+ Lenalidomide )
• Aggressive tumor –
R-CHOP /EPOCH-R
HCL • Males >50yrs • HPE- Hairy cell (circumferential hairy Tx - 1st line : Cladribine /
• Massive splenomegaly projection) in P/S, TRAP+ FludrabineQ
• Otherwise aymptomatic • BM aspiration – fried egg appearanceQ
• B-symptoms & LAN are rare • CD103+/ CD123+ / CD11c/ CD25 /
Annexin A1+Q
• Molecular study - BRAFV600E
mutationQ
CLL/SLL • Indolent neoplasm • Incidental finding • Variable
• Can transform into aggressive • Cytopenias – anemia (AIHA ) & • Indications for
tumor, into DLBCL → Richter’s thrombocytopenia (ITP) treatment –
Transformation @ rate of 5%/year • Recurrent infections - ↓gamma – Symptomatic
• Lots of B-symptoms & cytopenias globulins ƒ RAI 3/4 &
• Difference between CLL & SLL • Monoclonal gammopathy (5%) Binet c
depends on absolute lymphocyte • P/S- smudge cells + BMA /LN Bx- small ƒ LDT
count(ALC) round blue cells (lymphocyte
– CLL - if ALC >5000 +/- LAN / • Immunophenotypic marker - CD5+/ doubling time )
Hepatosplenomegaly (HSM) CD23+ /CD 200+ CD10- Q < 6 months
– SLL - if ALC < 5000 + LAN +/- • Cytogenetic marker- Or
HSM – FAVORABLE MARKERS ALC ↑↑ > 50 % in <2
• MBL - monoclonal B-cell ƒ 13q deletion – mcQ months
lymphocytes, ALC <5000, no LAN, ƒ Rb gene deletion ƒ Refractory
no HSM
ƒ Others- Zap70 - /CD38 /IgVH AIHA /
• RAI Staging used for CLL (mutated) refractory ITP
patients
– Unfavorable Markers ƒ Massive
– 0- ↑lymphocytosis splenomegaly
ƒ 17p deletion
– 1- LAN ƒ Bulky LN
ƒ 11q deletion (ATM )
– 2- HSM ƒ B-symptoms
ƒ IgVH (unmutated)
– 3- Anemia (present d/t AIHA) TOC–
ƒ Zap 70 +
– 4- Thrombocytopenia – 1st line BTK
ƒ CD38+
• Binet staging used for SLL inhibitors –
– Neutral Prognosis – Trisomy 12
patients ƒ Ibrutinib
– Binet A- <3 LN areas ƒ Acalabrutinib
– Binet B- ≥ 3 LN areas – 2nd line – Bcl 2
– Binet C- Anemia/ inhibitor
Thrombocytopenia ƒ Venetoclax

* For Making Notes

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Cerebellum Quick Revision Notes

Indolent T-Cell NHLs

NHL Presentation Clues Possible 1st line Rx
MF • Mc cutaneous T-cell lymphoma • Epidermotropic Variable
(CTCL) lymphocytes
• Skin +/- LAN • Haloed lymphocytes
• Patch →scaling lesion →plaque • Pautrier’s
→erythroderma microabscessQ
SS - leukemic • present with erythroderma & LAN • Sezary cells in Variable
transformation of P/ SQ (malignant
mycosis fungoides leukemic cells seen
in circulation that
have characteristic
cerebriform nucleus)
ATCL • HTLV-1 related Clover leaf like cells CHOP regimen / Mogamulizumab
• Indolent form to aggressive form (anti-CCR4 Mab)

↓ ↓
• Skin lesion leukemia + lytic
lesions
ALCL • LAN + HSM • ALK +/ CD30+ • EPOCH
• ↑risk with female & silicone breast • Cytogenetic marker- • Brentuximab vedotin (anti
implants t(2;5) ALK –NPM CD30 Mab)
fusion

Starry sky appearance Hairy cell leukemia - TRAP+

Hairy cell leukemia CLL – Smudge cells

* For Making Notes

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Medicine

Sezary cell Pautrier microabscess

PLASMA CELL DYSCRASIA

Clonal BMPC M-protein MDE

MGUS- <10% + (<3g/ml) -

• ↑risk of transformation to SMM
• M ≥ 1.5g/dlQ
• Abnormal SFLCR
• Non IgG MGUS
• No Tx. Observed
SMM >10%, <60% +/- ( ≥ 3g/ -
• No Tx. Observed dl)

MM ≥ 10% (50%- IgG / +/- (>3g/ +

• Tx: 1st line- Triple therapy + Daratumumab (anti CD38 Mab) 20% IgA /20% only dl ) • Myeloma defining event-
– especially if high risk light chains)
– SLIMQ –
• Marker of poor prognosis/ high risk- ƒ S - 60% of clonal
1. β2 microglobulin BMPC
2. Cytogenetic markers - t(4;14), t(14;16), t(14;20), 17p deletion ƒ LI - Light chains-
(p53deletion), 1q+ kappa/lambda
3. ↑LDH ≥ 2x upper limit (involved/ uninvolved
• Plasma cell leukemia – if absolute malignant plasma cell in P/S >100 + involved ≥
≥ 500 100mg %)
OR ƒ M - Whole body MRI
Differential count ≥ 5% (≥ 2 focal lesions) /
• Standard triple therapy – Whole body PET
1. Dexamethasone scan
2. Immunomodulator – Lenalidomide /Pomalidomide → ↑CNS – CRAB – Q
penetration ƒ Hypercalcemia
→ if 1 + 2 used together, ↑ risk of thromboembolic manifestations ƒ Renal dysfunction
3. Proteasome inhibitors-
ƒ Anemia
– Bortezomib → ↑risk of peripheral neuropathy
ƒ Bone Lytic lesions
– Carfilzomib
– Ixazomib
• AKI: causes –
– ↑↑ S. Creatinine d/t hypercalcemia
– Cast nephropathy
– Tx- IVF + chemotherapy – cyBorD regime (Dexamethasone +
Proteasome inhibitor + cyclophosphamide)
Plasmacytoma • None +/- (0.5g/ +
Types - * For Making
• Notes
If detectable dl)
1. Solitary bone plasmacytoma- mc, mc site is spine, ↑ risk of clonal BMPC
transformation, ↑ mortality rate - ↑ risk of
2. Solitary extramedullary plasmacytoma – mc sites are head & neck transformation
• Tx: local RT +/- Surgical excision to MM
174
Cerebellum Quick Revision Notes

WM (waldenstrom macroglobulinemia)
• Lymphoplasmacytoid lymphocytes

• C/f – old >70yrs age, familial predisposition

• Cytopenias/ B symptoms /HSM /Cold type

AIHA /Acquired VWD/ peripheral neuropathy
Myeloma cells Lytic lesions - MM
(anti MAG Ab)Q

• Tx – B-R regime- Bendamustine with Rituximab

• Alternative to Rituximab – Obinutuzumab

Features WM (waldenstrom MM
macroglobulinemia)
Monoclonal IgMQ IgM rare
Ig
Lytic lesion No CommonQ
HSM/LAN Common Rare
Hyper- ++ (common ) Rare
viscosity
SIg ++ -
CD20 ++ -
CD56 - ++
MYD88 ++ -

Serum Protein Electrophoresis coupled with serum im- mutations

mune fixation t(11;14) - Common,
marker or
standard risk

Important CMPNs
Parameter CML PV ET PMF
CBC WBC ↑↑↑ ↑ Normal ↑/↓
RBC
Normal /↓ ↑↑↑ Normal ↓
Platelets
↑/↓ ↑ ↑↑ ↑/↓
Smear Left shift Normal ↑ Platelets Leukoerythoblastic

pictureQ
LAP score ↓↓ Normal /↑ Normal /↑ Normal /↑
BMAx Cellularity ↑↑ /myeloid ↑↑/trilineage ↑↑/ megakaryoid ↑/↓
hyperplasia
Fibrosis +/- +/- Notes
* For Making +/- ++++
Megakaryocytes Hypolobated Pleomorphic Staghorn Bulbous
Molecular Ph+, t(9;22), BCR-ABLQ JAK-2 mutationQ JAK-2 mutation > JAK-2 > CALR >
V617F > Exon 12 CALR > CMPL CMPL
 175
Medicine

Parameter CML PV ET PMF

Clinical Asymptomatic / present • Vasomotor – erythromelagia / Cytopenias
with cytopenia and Aquagenic pruriritis
B-symptoms +
• Bleeding (↑ platelet > 15)/thrombosis
(↑WBC)
Splenomegaly Moderate - massive Mild Mild Moderate - massive
Management • 1st line- TKI Aspirin + phlebotomy Supportive therapy
Imatinib (s/e-edema)
In high risk
NR patients- Ruxolitinib
Target – male : <45% / Newer TKI like
T3151 mutation
– Female <42% Pacritinib Fedratinib
+
– Pregnant female <37% Momelotinib
Indication for cytoreductive therapy
Ponatinib
(↑thromboembolic (for ↑ risk)-
manifestations) 1. Age >6oyrs

Other 2nd/3rd gen. TKI 2. H/o thrombosis

Nilotinib/dasatinib(s/e - pleural3. PLT count >15lakhs
effusion) 2nd gen Bosutinib - 3rd For PV-
gen
• 1 line – HydroxyureaQ
st

• Triad for dx- ↑

WBCs with left shift
+ BMAx- myeloid
hyperplasia with ↑M:E Not tolerated/ C/I Ruxolitinib (JAK1/2
ratio + Ph+ (FISH & inhibitor)
Karyotyping)Q • In pregnant women - IFN
• Follow- up- PCR → For ET-
BCR-ABL mRNA • 1st line- Hydroxyurea
transcript
• Alternative- Anagrelide
• 3 STAGES-
1. Chronic phase - mc
presentation phase,
<10% blasts →
↑platelet / ↑basophilQ
2. Accelerated Phase
- 10-19% → ↓
platelets/↑↑basophils/
≥ 20%
3. Blast phaseQ - ≥ 20%
blasts
2/3rd →myeloid blasts
1/3rd →lymphoid blasts

* For Making Notes

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Cerebellum Quick Revision Notes

CML – leukocytosis + Left shift

Erythromelalagia

FISH – Ph+, BCR-ABL fusion

Tumor marker Cancer Non neoplastic conditions

Hormones
Human chorionic gonadotropin Gestational trophoblastic disease / Pregnancy
gonadal germ cell tumors
Calcitonin Medullary thyroid cancerQ
Catecholamines Pheochromocytoma
Oncofetal antigens
AFP HCC/ Gonadal germ cell tumorsQ Hepatitis / Cirrhosis
CEA Adenocarcinoma colon (Pancreas/ Pancreatitis / Hepatitis /IBD /
Breast) Smoking
Enzymes
Prostatic acid phosphatase Prostate cancer Prostatitis /BNP
Neuron –specific enolase Neuroblastoma /SCLC Q

Lactate dehydrogenase Lymphoma /Ewing sarcoma Hemolysis /MI/ Rhabdomyolysis/

Hepatitis
Tumor associated proteins
Prostate specific antigen Prostate cancers Prostatitis /BNP
Monoclonal immunoglobin MM/ WM MGUS/ infections -HCV
CA-125 Ovary Pregnancy /Menstruation /Peritonitis
CA-19-9 Pancreas/ colon /Breast Pancreatitis /UC
CD30 HL / ALCL
CD25 ATCL /HCL HLH

* For Making Notes

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Medicine

Syndrome Mechanism Features Cancers

SIADH ↑ADH → ↑H2O reabsorption Euvolemic hyponatriemia Q
SCLC/GI/GU
→ ↓Na ↓S.Na /↑U.Na /
↓S.Osm /↑U.Osm
Cushings ↑ACTH → ↑S.Cortisol Hyperpigmentation/ SCLC /Carcinoid
cushingoid /metabolic
hypokalemia
Hypercalcemia • PTHrP –mc, >80%Q Polyuria /dehydration +/- ↓ • SCC (Sq CC)/ RCC
• Lytic metastasis BP /AKI • Lytic metastasis – MM/any
• ↑1, 25 DHCC solid organ tumor
• Lymphomas
Osteomalacia ↑ FGF23 → ↑PO42- wasting Bone pain, fractures, Fibromas/ Sarcomas/
hypophosphatemia Hemangiopericytoma
Carcinoid syndrome ↑ serotonin Flushing /diarrhea/ pellagra Carcinoid /MTC (rarely)
/↑ urinary 5HIAA, ↑
S.Chromogranin A.
NICTH ↑IGF2 → hypoglycemia Whipple triad (↓insulin ) HCC/ Mesenchymal tumors
Male feminization ↑β-HCG →↑Aromatase Gynecomastia / Precocious Testicular cancer/ NSCLC
activity in leydig cells → puberty (Large cell cancer)
↑estrogen
Hypothyroidism T3 deiodinase , T4/T3 → ↓T4/T3 ,↑TSH , ↑r T3 Hemangiomas
rT3
Limbic encephalitis Anti HU Ab/ Anti CRMP5 • Subacute presentation , • SCLC (anti HU Ab ,
Ab / Anti Ma2 Ab/ Anti psychiatric / behavioural anti CRMP5 Ab, anti
GAD Ab/ Anti amphiphysin changes, with refractory amphiphysin Ab, anti
Ab/ Anti NMDA Ab/ Anti seizures with memory AMPA)
AMPA Ab loss • Testicular cancer –anti MA
• MRI- hyperintensities in 2 Ab
B/L medial temporal lobe • Overian teratoma (anti
• EEG- Extreme δ brush NMDA Ab)
Cerebellar degeneration Anti Yo Ab /Anti Hu Ab / • Anti Yo Ab - Breast/Ovary
Anti Ri Ab/ Anti Tr (DNER) cancer
Ab / Anti MGLUR Ab/ Anti • Anti Hu Ab, Anti Ri Ab-
VGCC Ab SCLC, Anti Tr Ab, Anti
MGLUR Ab-HL, Anti VGCC
Ab-SCLC
Other CNS syndromes Anti amphiphysin Ab /Anti • Anti amphiphysin Ab /Anti
GAD Ab , Anti AchR Ab Anti GAD Ab – SPS
VGCC Ab • Anti AchR Ab – Myasthenia
gravis
• Anti VGCC Ab - LEMS
Polycythemia ↑↑EPO Asymptomatic +/- RCC/HCC /Cerebellar
hyperviscosity features +/- hemangioblastomaQ
thrombosis
* For Making Notes
178
Cerebellum Quick Revision Notes

IMPORTANT ONCOLOGIC EMERGENCIES

1. Tumor lysis syndrome
• d/t hematological cancer → eg – BL/DLBCL
• Aute leukemia (ALL > AML) → ↑↑ WBCs
• If LDH ≥ 2x upper limit → high risk
• C/F-
– hyperuricemia → MSU crystals → AKI
– hyperkalemia → Arrythmias
– hyperphosphatemia
CaPO4 → AKI
– hypocalcemia

Tetany → seizure

• Tx – IVF + Rasburicase (C/ in G6PD deficiency) +/- Renal replacement therapy

• Prevention – IVF + Allopurinol/Rasburicase

• Urinary alkalinisation to be avoided

2. Epidural spinal cord compression

• Cancer + back pain → neurological examination → if deficit – Urgent whole spine MRI
• Tx- dexamethasone
If normal

X-ray spine

Red flag – back pain with coughing

No
Supportive care with analgesic

3. SVC Syndrome
• d/t compression of SVC by cancer
• mcc – NSCLCL
• C/F- edema of face/neck/arms + dilation of chest veins + JVD with pulsations – HJR +/- ↓BP/SOB,
↓spO2 + Headche /altered mental status IOC- CECT chest

* For Making Notes

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Medicine

Mx- if severe symptoms

Yes
catheter venography 4. Febrile neutropenia – fever + ANC
<500Q
SVC obstruction • Mcc – gram positive cocci >70% cases
• TOC – Piptazo
No Balloon angioplasty /stenting of – Meropenem any 1 +/- cover risk factor
superior VC
– Cefepime
→ MRSA Cover - ↓BP / ARDS +/- MRSA →
Vancomycin
lx- CECT Tx of cancer
→ Antifungal cover - no resolution of fever
→ Voriconazole/ L-AMB/ Echinocandins

* For Making Notes

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 Chapter - 8 Hematology

DRUGS AFFECTING BLOOD FLOW

ANTI PLATELET DRUGS

Warfarin Overdose:
1. Aspirin Inhibit COX → ↓TXA2
2. Clopidogrel Acts on ADP • Overdose of Warfarin causes bleeding
Ticlopidine • Active Factors like IIa, VIIa, IXa, Xa (which are
3. Abciximab Act on GP IIb/IIIaQ Known as Four Factor complex (or) Prothrombin
Factor complex) is the Treatment of choice.Q
Tirofiban
Eptifibatide • If Four Factor complex is not available, then fresh
frozen plasma can be used.
4. Atopaxar Act on PAR-1 receptors of
Vorapaxar thrombinQ • If the fresh frozen plasma is also not available,
whole blood should be given
ANTI COAGULANTS • But the Treatment of choice for bleeding tendency
due to warfarin is Vitamin K
These are divided into oral and parenteral anticoagulants
• Vitamin K is also antidote for Warfarin overdose.
Oral Anti-Coagulants
• Vitamin K inhibitors
2. Direct Thrombin Inhibitors
• Direct thrombin inhibitors
• Dabigatran - Can be given Orally and does not
• Factor Xa inhibitor require monitoringQ

1. Vitamin K inhibitors 3. Direct factor Xa inhibitors

→ Includes dicumarol and warfarin Drugs are
Properties of Warfarin: • Rivaroxaban RIVAR – REVERSIBLE
1. Oral anticoagulant • Apixaban O – ORAL
2. Inhibit vitamin - K XA – XA
• Edoxaban
B – BLOCKER (OR)
3. Takes 4-5 days to produce action • Betrixaban AN – ANTAGONIST
4. Mainly used for maintenance purpose
5. Contraindicated in pregnancy
6. Effect of Warfarin is monitored by PT/INR
 61
Pharmacology

Injectable Anti-Coagulants FIBRINOLYTIC DRUGS

1. Indirect Thrombin Inhibitors • All drugs in this group are tissue plasminogen
2. Direct Thrombin Inhibitors activators.
1. Indirect Thrombin Inhibitors [Heparin] • tPA converts plasminogen to plasmin that breaks the
thrombus
UFH Activate Inhibit factor IIa = Xa
• These are used for acute MI, acute stroke and acute
antithrombin
DVT
LMWH Activate Inhibit factor Xa > llaQ
antithrombin → Drugs
Fondaparinux Activate Only inhibits factor Xa Q S – Streptokinase
antithrombin U – Urokinase
R – Reteplase
A – Alteplase
Heparins T – Tenecteplase
1. Route → S.C. or IV
2. Activate anti-thrombin Overdose of thrombolytics
3. Immediate Action → Useful in acute conditions
→ Leads to bleeding
4. Anti-coagulant of choice in pregnancy
→ Antidotes:
5. Monitoring done by a PTT
– Epsilon Amino Caproic Acid [EACA]
6. Antidote → Protamine Sulphate
– Tranexamic Acid.
WARFARIN HEPARIN
Route Oral S/C or IV
DRUGS AFFECTING BLOOD CELLS
MOA Inhibit vitamin K Activate AT – III
Onset 4-5 days Immediate • Hematinics
Use Maintenance Acute condition
• Growth factors
Pregnancy C/I DOC
Monitoring PT/INR aPTTQ HEMATINICS
Antidote Vitamin K Protamine These are nutritional substances which help in formation
2. Direct Thrombin Inhibitors (DTI) of blood. e.g.
1. Iron (Fe)
• Bivalirudin, argatroban and melagatran are injectable 2. Folic acid (FA)
DTI.Q 3. Vitamin B12
• Hirudin and lepirudin are not used now
Iron Deficiency Anemia
• These are DOC for heparin induced thrombocytopenia
• Treatment of choice is Oral iron.
(HIT)
Oral Iron
ANTIDOTES OF ANTI-COAGULANTS • Various preparations like ferrous sulphate, ferrous
Antidote Anticoagulant fumarate are available.
Vitamin K Warfarin – For adults, tablets are given
Protamine sulfate HeparinQ
– For children drops are available. These should
Idarucizumab DabigatranQ
be given deep in mouth or else they cause skin
Andexanet-Alpha Factor Xa inhibitors e.g., Apixaban pigmentation
• Earliest response - ReticulocytosisQ
• If Hb is improving by 0.5 g/dl/week, that means
adequate response
62
Cerebellum Quick Revision Notes
• Oral iron treatment is continued for 2-3 months Injectable Iron
even after the Hb levels come to normal to replenish
• Preparations of injectable iron are:
the iron stores in body.
– Iron Dextran –Can be given IV as well as IM
• Factors affecting
– Iron Sorbital citrate (Used IM only)
– Ascorbic acid : Increase Absorption
• Intramuscular iron is given by Z-tract technique to
– Phytates and oxalates :Decrease Absorption
avoid pigmentation

HEMATOPOIETIC GROWTH FACTORS

Cells Growth Factor Drug Indications
RBC Erythropoietin Darbopoietin Anemia due to chronic renal failure
Anemia due to bone marrow suppression
WBC G-CSF Filgrastim Leukopenia due to bone marrow suppression
GM-CSF Sargramostim
Platelets IL-11 Oprelvekin Thrombocytopenia due to bone marrow suppression

Previous Years Questions

Q1. Which of the following is an oral direct thrombin
inhibitor?

A. Dabigatran B. Rivaroxaban
C. Warfarin D. Lepirudin

Q2. What is the mechanism of action of tPA?

A. Fibrinolysis
B. Inhibition of factor V and VII
C. Inhibition of factor III and V
D. Activation of anti-thrombin III

Q3. A female patient was taking warfarin for prosthetic

heart valves. She became pregnant. What advise will
you give regarding use of this drug in early pregnancy? A. Clopidogrel B. Heparin
A. Continue warfarin without any concern C. Dicumarol D. Alteplase
B. Continue warfarin but add vitamin K to the therapy Q5. A patient presented to hospital with chest pain.
C. Change warfarin to heparin ECG of the patient confirms it to be non ST elevation
myocardial infarction. Which of the following drug useful
D. Terminate the pregnancy in this patient acts by inhibiting platelet aggregation?
Q4. In the given diagram, identify drug Z marked by A. Clopidogrel B.Streptokinase
the arrow
C. Low molecular weight heparin D.Warfarin

Answers
1. - A 3. - C 5. - A
2. - A 4. - C
 63
Pharmacology
Q6. A deep vein thrombosis patient was started on an Drug A Drug B Drug C
anticoagulant therapy. Next day, the patient presented
a Aspirin Vorapaxar Prasugrel
with the features shown in the diagram below. Likely
drug implicated for this adverse effect is b Dipyridamole Eptifibatide Vorapaxar
c Aspirin Eptifibatide Prasugrel
d Dipyridamole Prasugrel Eptifibatide

Q10. Which of the following statements is most correct

regarding mechanism of action of dicumarol?

A. It acts as a calcium chelator and reduces the

A. Heparin B. Rivaroxaban availability of calcium in coagulation pathway

C. Warfarin D. Dabigatran B. It binds and activates anti-thrombin 3 that

accelerates its interaction with thrombin and factor Xa
Q7. Among the following drugs, oral factor Xa inhibitor resulting in their degradation
is: C. It acts as a Vitamin K inhibitor that results in
A. Dabigatran etexilate B. Rivaroxaban inhibition of activation of clotting factors 2,7,9 and 10

C. Fondaparinux D. Bivalirudin D. It inhibits tissue plasminogen activator resulting in

stoppage of conversion of plasminogen to plasmin
Q8. A 45 year old patient being treated with low dose
aspirin since 6 months presented with rectal bleeding.
Inhibition of which of the following substance is likely Q11. Vitamin that increases the absorption of iron from
to responsible for the bleeding? stomach is?
A. Vitamin A B. Vitamin B12
A. TXA2 B. LT
C. Vitamin C D. Vitamin D
C. Bradykinin D. PGI2
Q12. Excessive phytates intake in the diet may lead to
Q9. Mechanism of action of some antiplatelet drugs is deficiency of
shown in the given diagram. Which of the following is A. Proteins B. Iron
correct match:
C. Vitamin B12 D. Vitamin D
Q13. Indication for use of Pegylated Filgrastim is in the
correction of:
A. Anaemia B. Neutropenia
C. Thrombocytopenia D. Pancytopenia

Answers
6. - C 8. - A 10. - C 12. - B
7. - B 9. - C 11. - C 13. - B
 Chapter - 9 Gastrointestinal Tract
PEPTIC ULCER DISEASE Adverse Effects (on long-term use)
→ Due to excessive acid in stomach • ↓ Ca2+ [Osteoporosis]
Treatment • ↓ Vit B12 [Megaloblastic anaemia]Q

1. ↓ ACID • ↑ Infections
→ HCl produced by Parietal cell of stomach
→ Proton Pump [H+-K+-Pump] helps in secretion of acid 2. ANTACIDS
– Stimulated by → Fastest pain relievers of PUD
ƒ ACh [M1] → Include
– AI [OH]3 → Cause constipation
ƒ Histamine [H2]
– Mg [OH]2 → Cause Diarrhoea
ƒ Gastrin [CCK] → Given in combination
– Inhibited by PGE2
Drugs ↓ Acid 3. ULCER PROTECTIVE DRUGS
M1 blockers H2 blockers PGE2 PPI → Sucralfate
Pirenzepine Cimetidine Misoprostol Omeprazole → Sucralfate acts by Polymerization, requires acidic
Telenzepine Ranitidine Esomeprazole pH [<4]
Famotidine Pantoprazole – Should not be combined with antacids
Loxatidine Lansoprazole → Inhibits absorption of several drugs like
Rabeprazole phenytoin. So, a gap of minimum 120 minutes
should be kept between two drugs

Most specific drug for NSAID

MisoprostolQ
induced Peptic ulcer
DOC for NSAID induced Peptic
Proton Pump lnhibitorsQ
ulcer

PPls [Proton Pump Inhibitors]

• Irreversible inhibitors
• Example of Hit and Run Drugs
• Exert systemic effect [Do not work locally]
4. ANTI-H. PYLORI DRUGS
• Given with acid resistant coating (Enteric coating)
• Amoxycillin
• Metronidazole
Indications • Clarithromycin
• DOC for PUD due to any reason
Triple Drug Therapy
• DOC for GERD
• Used for H. pylori associated PUD
• DOC for Zollinger Ellison Syndrome
• PPI + 2AMA used
C → Clarithromycin Preferred triple drug therapyQ
A → Amoxycillin Given for 2 weeks

P → PPI
 65
Pharmacology

ANTI-EMETIC DRUGS PROKINETIC DRUGS

1. Chemotherapy induced nausea and vomiting (CINV):
→ Used in GERD
Type Drug of Choice
→ Drugs are
Early CINV 5HT3 antagonistsQ
- Ondansetron 1. D2 Blockers
• Domperidone
- Granisetron
• Metoclopramide
- Palonosetron
Delayed CINV Substance P antagonistsQ
2. 5HT4 Agonist

- Aprepitant
• Mosapride
• Prucalopride
- Rolapitant
3. Motilin Receptor Agonist
2. D2 Blockers • Erythromycin

Metoclopramide DomperidoneQ
Cross BBB Do not cross BBB
Can cause dystonia Do not cause dystonia
DOC for Levodopa induced vomiting

Previous Years Questions

Q1. A patient on phenytoin for seizure disorder Q4. A patient presented to hospital with three bouts
was prescribed sucralfate 4 times a day for peptic of vomiting and treated with anti-emetic drug. Vomiting
ulcer. What should be the minimum duration between subsided but after sometime, he developed abnormal
consumption of two drugs? movements. Which of the following drug is used for
treatment of these motor symptoms?
A. 30 min B. 60 min
A. Benzhexol B. Cyproheptadine
C. 90 min D. 120 min
C. L-dopa D. Hyoscine
Q2. A female with ovarian cancer was on cisplatin
therapy. He presented to hospital with several episodes Q5. A patient is planned to receive chemotherapy with
of vomiting. After giving an antiemetic drug, the patient cisplatin. Which of the following drugs are used for
developed dystonia. The anti-emetic drug most likely to the treatment of chemotherapy induced nausea and
be responsible for these features is vomiting

A. Metoclopramide B. Meclizine A. Granisetron, aprepitant and dexamethasone

C. Ondansetron D. Scopolamine B. Metoclopramide, dexamethasone and domperidone
C. Prochlorperazine, granisetron and domperidone
Q3. Which of the following is not a prokinetic?
D. Promethazine, doxylamine and metoclopramide
A. 5HT4 agonist B. D2 blocker
C. Macrolides D. Diphenoxymethane

Answers
1. - D 3. - D 5. - A
2. - A 4. - A