#DAVIDSON_REVIEW

#HEMATOLOGY 1
Page 914-923
Anatomy & physiology *****
Fig 23.5 *****
Fig 23.6 ***
Box 23.2 **********
Box 23.3 *****
Box 23.5 ***
Box 23.7 **
FIG 23.5
+ SBA/MCQ
Right shift/ increasd O2 delivery/Reduced O2 affinity
Increased CADET
C - Co2
A - Acidosis / Increased H2
D - DPG/BPG
E - Exercise
T - Temperature
Left shift / Decreased O2 delivery/ Increased o2 affinity
Decreased CADET +
Methemoglobin
Fetal Hb
FIG 23.6
+ SBA/MCQ
+ এই figure এ physiology এর জন্য অনেক information আছে।যতটু কু পারেন পড়ে নিবেন।
IMPORTANT
*** VASCULAR ENDOTHELIUM produces substances (including NITRIC OXIDE,
PROSTACYCLIN AND HEPARANS) to PREVENT ADHESION OF PLATELETS AND
WHITE CELLS to the vessel wall.
* Platelets and coagulation factors circulate in a non-activated state
*** Platelets bind to collagen via a specific receptor, glycoprotein Ia (GPIa), binding of receptors
GPIb and GPIIb/IIIa to von Willebrand factor and fibrinogen respectively
*** FIBRIN monomers are cross-linked by FACTOR XIII, which is also activated by thrombin
(SBA)
Box 23.2
+ SBA/MCQ
+ এই বক্সের কোন কিছু বাদ দেওয়া যাবে না
+ সরাসরি SBA/MCQ থাকতে পারে
+ Scenario দিয়ে PBF findings দেওয়া থাকতে পারে।
BOX 23.3
+ SBA/MCQ
+ এই বক্সের ও কোন কিছু বাদ দেওয়া যাবে না
+ কি কি Investigation করা হয়? Notmal range কত? কোন কোন condition এ বাড়ে?
BOX 23.5
+ MCQ/SBA
*** Unusual sites of venous thrombosis
ANATOMY & PHYSIOLOGY
Hematopoiesis
*** During development, haematopoiesis occurs in the yolk sac, liver and spleen, and
subsequently in red bone marrow in the medullary cavity of all bones
* In childhood, red marrow is progressively replaced by fat (yellow marrow)
*** In adults, normal haematopoiesis is restricted to the vertebrae, pelvis, sternum, ribs,
clavicles, skull, upper humeri and proximal femora
* In normal marrow, nests of red cell precursors cluster around a central MACROPHAGE,
which PROVIDES IRON and also phagocytoses nuclei from red cells prior to their release into
the circulation
*** Plasma cells are antibody-secreting MATURE B CELLS that normally represent LESS
THAN 5% of the marrow population
*** All blood cells are derived from pluripotent haematopoietic stem cells (SBA)
RBC
*** The first non-nucleated red cell is a reticulocyte (SBA)
which still contains ribosomal material in the cytoplasm, giving these large cells a faint blue
tinge (‘POLYCHROMASIA’).
*** Reticulocytes lose their ribosomal material and mature over 3 days
*** Proliferation and differentiation of red cell precursors is stimulated by ERYTHROPOIETIN,
a POLYPEPTIDE hormone produced by RENAL INTERSTITIAL PERITUBULAR cells in
response to HYPOXIA (SBA)
(Erythropoietin - glycoprotein? )
* Normal mature red cells circulate for about 120 days. They are 8 μm biconcave discs
LACKING A NUCLEUS but filled with haemoglobin, which delivers oxygen to the tissues
** Red cells are exposed to osmotic stress in the pulmonary and renal circulation
*** In the ABSENCE OF MITOCHONDRIA, the energy for these functions is provided by
ANAEROBIC GLYCOLYSIS AND THE PENTOSE PHOSPHATE PATHWAY in the
HEMOGLOBIN
** Protein specially adapted for oxygen transport, composed of four globin chains, each
surrounding an iron-containing porphyrin pigment molecule termed haem
*** Haemoglobin A (αα/ββ) represents over 90% of adult haemoglobin, whereas haemoglobin F
(αα/γγ) is the predominant type in the fetus
* Each haem molecule contains a ferrous ion (Fe2+), to which oxygen reversibly binds; the
affinity for oxygen increases as successive oxygen molecules bind. When oxygen is bound, the
beta chains ‘swing’ closer together; they move apart as oxygen is lost. In the ‘open’
deoxygenated state, 2,3-bisphosphoglycerate (2,3-BPG), a product of red cell metabolism, binds
to the haemoglobin molecule and lowers its oxygen affinity
*** Haemoglobin F is unable to bind 2,3-BPG and has a left-shifted oxygen dissociation curve,
which, together with the low pH of fetal blood, ensures fetal oxygenation
* Strong oxidising agents, such as dapsone can convert ferrous iron in haemoglobin to its ferric
state (Fe3+)
*** Alpha globin chains are produced by two genes on chromosome 16, and beta globin chains
by a single gene on chromosome 11 (SBA)
** imbalance in the production of globin chains results in the thalassaemias . Defects in haem
synthesis cause the porphyrias
** Free intravascular haemoglobin is toxic and is normally bound by HAPTOGLOBINS, which
are plasma proteins produced by the LIVER.
WBC
** Granulocytes (neutrophils, eosinophils and basophils),
*** The first recognisable granulocyte in the marrow is the myeloblast (SBA)
* Myelocytes or metamyelocytes are normally found only in the marrow but may appear in the
circulation in infection or toxic states
NEUTROPHIL
* containing 2–5 segments and granules in their cytoplasmEvery day
** some 10^11 neutrophils enter the circulation
* exercise or catecholamines increase the number of cells flowing in the blood.
*** Neutrophils spend 6–10 hours in the circulation before being removed, principally by the
spleen
EOSINOPHILS
** phagocytic, intracellular killing of protozoa and helminths . They are also involved in allergic
reactions (e.g. atopic asthma
BASOPHILS
** Mast cells resemble basophils but are found only in the tissues
** These cells are involved in hypersensitivity reactions
MONOCYTES
*** Monocytes are the largest of the white cells (SBA)
LYMPHOCYTES
*** Lymphoid cells that migrate to the thymus develop into T cells, whereas B cells develop in
the bone marrow
*** The majority (about 80%) of lymphocytes in the circulation are T cells.
PLATELET
*** Platelets are formed in the bone marrow from MEGAKARYOCYTES
*** formation and maturation of megakaryocytes is stimulated by THROMBOPOIETIN
produced in the Liver
** circulate for 8–10 days before they are destroyed in the reticuloendothelial system
* Some 30% of peripheral platelets are normally pooled in the spleen and do not circulate
** Coagulation occurs by two pathways: it is initiated by the extrinsic (or tissue factor) pathway
and amplified by the ‘intrinsic pathway’
** Clotting factors are synthesised by the liver, although factor V is also produced by platelets
and endothelial cells
*** FACTORS II, VII, IX AND X require post-translational CARBOXYLATION to allow them
to participate in coagulation. The carboxylase enzyme responsible for this in the liver is
VITAMIN K-DEPENDENT. Vitamin K is converted to an epoxide in this reaction and must be
reduced to its active form by a REDUCTASE enzyme. This reductase is INHIBITED BY
WARFARIN
*** Warfarin inhibitis reductase enzyme > inhibtion of Vitamin k activation > Inhibition of
carboxylase enzyme activation > No activation of factor II,VII,IX,X > No activation of extrinsic
pathway > Increased PT
( + Extrinsic pathway assessed by PT)
BLEEDING DISORDERS
*** The tissue factor (‘extrinsic’) pathway is assessed by the prothrombin time (PT), and the
‘intrinsic’ pathway by the activated partial thromboplastin time (APTT), sometimes known as
the partial thromboplastin time with kaolin (PTTK)
*** BOTH PT AND APTT ARE PROLONGED, - deficiency or inhibition of the f inal
COMMON PATHWAY (WHICH INCLUDES FACTORS X, V, PROTHROMBIN AND
FIBRINOGEN) or global coagulation factor deficiency involving more than one factor, as occurs
in disseminated intravascular coagulation (DIC)
*** Platelet function has historically been assessed by the BLEEDING TIME, measured as the
time to stop bleeding after a standardised incision
*** Platelet function can be assessed in vitro by measuring AGGREGATION IN RESPONSE
TO ADRENALINE (EPINEPHRINE), COLLAGEN, THROMBIN, ARACHIDONIC ACID
AND ADP, AGGLUTINATION IN RESPONSE TO RISTOCETIN or by measuring the
constituents of the intracellular granules, e.g. adenosine triphosphate, adenosine diphosphate and
their ratio to each other (ATP/ADP)
** Monitoring of heparin therapy is required only with unfractionated heparins.
*** Low-molecular-weight heparins have such a predictable dose response that monitoring of
the anticoagulant effect is not required, except in patients with renal impairment (GFR less than
30 mL/min)
*** When monitoring is indicated, an ANTI-Xa activity assay rather than APTT should be used
(SBA)

#DAVIDSON_REVIEW
#HEMATOLOGY 2
Page : 923 - 930
Box 23.7 **
Fig 23.10/11 ***
Box 23.8 *****
Box 23.9 **********
Box 23.11 ***
Box 23.12 ***
Box 23.13 *****
Box 23.14 ***
Box 23.15 *****
Box 23.16 *****
*** Iron deficiency anaemia is the most common type of anaemia worldwide
*** H/0 previous surgery (e.g. resection of stomach or small bowel) + Anemia >>>
Malabsorption of iron and/or vitamin B12)
*** A normal MCV (normocytic anaemia) suggests either acute blood loss or the anaemia of
chronic disease, also known as the anaemia of inflammation (ACD/AI)
*** A low MCV (microcytic anaemia) suggests iron deficiency or thalassaemia or sometimes
ACD/AI
*** A high MCV (macrocytic anaemia) suggests vitamin B12 or folate deficiency or
myelodysplasia
Fig 23.10 & 11
+ SBA
কিভাবে পড়বেন
*** MCV এর value পড়বেন Normal/low/increased
Scenario তে anemia এর কিছু features (Page 913) দেওয়া থাকবে & PBF/CBC findings. Dx, Inv,inv
finding?
*** Low MCV + Low MCH + Low ferritin >>> Iron deficiency anemia
*** low MCV + Low MCH + Target cells /& Basophilic stippling >> Do Hb electrophoresis
+ Normal HbA2 >> Alpha trait
+ Increased Hb A2 >> B trait
*** High MCV + Hypersigmented Neutrophil >> B12/Folate Deficiency/Megaloblastic anemia
Box 23.8
+ MCQ
+ Box এর সব কিছু পড়বেন
+ Absolute & relative এ কি কি feature পাবেন
*** Secondary causes Specially conditions of increased erythropoietin secretion
** Males and females with Hct values of over 0.60 and over 0.56, respectively, can be assumed
to have an absolute erythrocytosis
**" In polycythaemia rubra vera (PRV), a mutation in a kinase, JAK-2 is found in over 90% of
cases (SBA)
*** Patients with PRV have an increased risk of arterial thromboses, particularly stroke, and
venous thromboembolism. They may also have aquagenic pruritus (itching after exposure to
water), hepatosplenomegaly and gout (due to high red cell turnover)
** Neutropenia A reduction in neutrophil count (usually < 1.5 × 109/L. Counts lower than 0.5 ×
109/L considered to be critically low.
** Lymphopenia : This is an absolute lymphocyte count of less than 1 × 109/L.
** Eosinophilia : A high eosinophil count of more than 0.5 × 109/L . Eosinophil infiltration can
damage many organs (e.g. heart, lungs, gastrointestinal tract, skin, musculoskeletal system)
** Lymphocytosis : greater than 3.5 × 109/L
(বাকি গুলার value physio বই/গাইড থেকে দেখে নিবেন)
BOX 23.9
+ MCQ
+ Difficult but you have to read
*** ডান পাশের গুলা বেশি গুরুত্বপূর্ণ।।
Box 23.11
+ MCQ / SBA
*** Phenytoin
*** For SBA REMEMBER
*** Nodes that enlarge in response to local infection or inflammation (‘reactive nodes’) usually
expand rapidly and are painful, whereas those due to haematological disease are more frequently
painless
***Nodes involvement
• the scalp, ear, mouth and throat, face, teeth or thyroid for neck nodes
• the breast for axillary nodes
• the perineum or external genitalia for inguinal nodes
*** Generalised lymphadenopathy may be secondary to infection, often viral, connective tissue
disease or extensive skin disease (dermatopathic lymphadenopathy) but is more likely to signify
underlying haematological malignancy
*** Weight loss and drenching night sweats that may require a change of nightclothes are
associated with haematological malignancies, particularly lymphoma (SBA)
So
Rapid,painful & localized lymphadenopathy >>> Think infective cause first
Painless, slow & generalised lymphadenopathy >>> Think hematological Malignancy first
Box 23.12
+ MCQ
+ Need to read all
For SBA keep in mind
*** Cardiac, infective, inflammatory & myeloproliferative causes
*** Find the causes of massive splenomegaly *
Box 23.13
+ SBA/MCQ
BLEEDING
1 *** Bleeding into muscle and joints, along with retroperitoneal and intracranial haemorrhage,
indicates a likely defect in coagulation factors ( Ex - Hemophilia, Warfarin therapy,Coagulation
factor deficiency)
2 *** Bleeding from superficial cuts, epistaxis, gastrointestinal haemorrhage or menorrhagia is
more likely to be due to thrombocytopenia, a platelet function disorder or von Willebrand
disease.
3 *** Recurrent bleeds at a single site suggest a local structural abnormality rather than
coagulopathic bleeding
(Scenario Dx er সময় এই ৩ টা পয়েন্ট খেয়াল রাখবেন।Bleeding site টা কোথায় বলা হচ্ছে।)
** Petechial purpura is minor bleeding into the dermis that is flat and non-blanching (
** Ecchymosis, or bruising, is more extensive bleeding into deeper layers of the skin. The
lesions are initially dark red or purple but become yellow as haemoglobin is degraded
THROMBOCYTOPENIA
** Spontaneous bleeding does not usually occur until the platelet count falls below 20 × 109/L
** Platelet transfusion is rarely required and is usually confined to patients with bone marrow
failure and platelet counts below 10 × 109/L, or to clinical situations with actual or predicted
serious haemorrhage.
THROMBOCYTOSIS
*** The most common reason for a raised platelet count is that it is reactive to another process,
*** Reactive thrombocytosis is distinguished from the myeloproliferative disorders by the
presence of uniform small platelets, lack of splenomegaly, and the presence of an associated
disorder.
Box 23.14
+ MCQ
*** Increased consumption, immune mediated causes
*** Associated conditions of ITP *
Box 23.15
+ SBA/MCQ
*** Reactive causes
Box 23.16
+ MCQ
#DAVIDSON_REVIEW
#HEMATOLOGY 3
Page 931 - 940
Box 23.17 **
Fig 23.14 **
Box 23.18 **
Box 23.22 ***
Box 23.23 ***
Box 23.24 ***
HEPARIN *********
Box 23.26 ***
Box 23.27 **********
Box 23.28 *** ( Contraindications only)
Box 23.29 **********
Box 23.17
+ SBA / MCQ
( Also Important for clinical practice )
IMPORTANT
Red cell concentrate
• If no cardiovascular disease, transfuse to maintain Hb at 70 g/L
• If known or likely to have cardiovascular disease, maintain Hb at 90 g/L
Platelet concentrate
• Each adult dose raises platelet count by 40 × 109/L unless there is consumptive coagulopathy,
e.g. disseminated intravascular coagulation
• Maintain platelet count > 50 × 109/L, or in multiple or central nervous system trauma > 100 ×
109/L
• Maintain platelet count > 10 × 109/L if not bleeding
• Maintain platelet count > 20 × 109/L if minor bleeding or at risk (sepsis, concurrent use of
antibiotics, abnormal coagulation)
• Increase platelet count > 50 × 109/L for minor invasive procedure (e.g. lumbar puncture,
gastroscopy and biopsy, insertion of indwelling lines, liver biopsy, laparotomy) or in acute,
major blood loss
• Increase platelet count > 100 × 109/L for operations in critical sites such as brain or eyes
FFP
• Replacement of coagulation factor deficiency
*** Thrombotic thrombocytopenic purpura
Cryoprecipitate
*** Fibrinogen , Factor VIII, von Willebrand factor
*** Indication : von Willebrand disease and haemophilia
Fog 24.14
*** Test for: HIV,HTLV,Hepatitis B, Hepatitis C, Hepatitis E ,Syphilis ,ABO + RhD ,Other
blood groups ,Red cell antibodies
*** Storage :
• RBC : 4°C / 35 days
• FFP : –30°C/36 months
• Platelets : 22°C / 5 days
Box 23.24
+ SBA /MCQ
+ Infection & time
*** CMV, Pneumocystis jiroveci
** Acute GVHD occurs in the first 100 days after transplant in about one-third of patients. It can
affect the skin, causing rashes, the liver, causing jaundice, and the gut, causing diarrhoea, and
may vary from mild to lethal.
ANTICOAGULANT AND ANTITHROMBOTIC THERAPY
*** Antiplatelet medications are of greater efficacy in the prevention of arterial thrombosis and
of less value in the prevention of venous thromboembolism
warfarin and other anticoagulants are favoured in VTE and management of atrial fibrillation
Box 23.25
+ INR 2.5 in most cases except two where it's 3.5 ( remember this 2 indication)
HEPARIN *********
LMWHs ***
• Nearly 100% bioavailable and so produce reliable dose-dependent anticoagulation
• Do not require monitoring of their anticoagulant effect (except possibly in patients with very
low body weight and with a glomerular filtration rate below 30 mL/min)
• Half-life of around 4 hours when given subcutaneously, compared with 1 hour for UFH
• Risk of osteoporosis and heparin-induced thrombocytopenia is much lower for LMWH
UFH
*** More completely reversed by protamine sulphate (SBA)
*** Cardiopulmonary bypass UFH remains the drug of choice
Useful in
• Patients with a high risk of bleeding, e.g. those who have peptic ulceration or who may require
urgent surgery. It is also favoured in the treatment of
• Life-threatening thromboembolism, e.g. major pulmonary embolism with significant
hypoxaemia, hypotension and right-sided heart strain
HEPARIN-INDUCED THROMBOCYTOPENIA
*** Caused by induction of anti-heparin/PF4 antibodies (SBA)
*** This results in platelet activation and a prothrombotic state, with a PARADOXICAL
THROMBOCYTOPENIA
• HIT is more common in surgical than medical patients (especially cardiac and orthopaedic
patients), with use of UFH rather than LMWH, and with higher doses of heparin
Clinical features
• typically 5–14 days after starting heparin
• fall in platelet count of more than 30% from baseline.
*** Confirmed or refuted using an anti-PF4 enzyme-linked immunosorbent assay (ELISA).
(SBA)
COUMARINS
*** Inhibit the vitamin K-dependent post-translational carboxylation of factors II (prothrombin),
VII, IX and X in the liver
• Warfarin anticoagulation typically takes more than 3–5 days to become established, even using
loading doses
The major problems with warfarin are:
• a narrow therapeutic window
• metabolism that is affected by many factors
• numerous drug interactions.
Management of warfarin
• vitamin K
• prothrombin complex concentrate that contains factors II, VII, IX and X
• Fresh frozen plasma
Box 23.27
*** ALL ARE IMPORTANT FOR SBA
Reversal of life- and limb-threatening haemorrhage in anticoagulated patients:
• Warfarin: prothrombin complex concentrate and IV vitamin K1
• Unfractionated heparin: protamine sulphate
• Dabigatran: idarucizumab
• Thrombotic thrombocytopenic purpura : plasma exchange
• Coagulopathy associated with acute promyelocytic leukaemia : all-trans-retinoic acid and
fibrinogen replacement
• eutropenicrome and stroke in patients with sickle-cell anaemia : red cell transfusion or
exchange transfusion
• Neutropenic sepsis in patients receiving chemotherapy : Empirical broad-spectrum antibiotics
Box 23.29
HAEMATOLOGICAL PHYSIOLOGY IN PREGNANCY
IMPORTANT
FULL BLOOD COUNT:
• increased plasma volume (40%)
• lowers normal haemoglobin
• Mean cell volume (MCV) may increase by 5 fL
• Neutrophilia
• Gestational thrombocytopenia - benign phenomenon
• Depletion of iron stores, Vitamin B12, Folate
COAGULATION FACTORS:
• From the SECOND trimester, procoagulant factors increase approximately threefold,
particularly FIBRINOGEN, VON WILLEBRAND FACTOR AND FACTOR VIII
• Activated protein C resistance
• Shortened activated partial thromboplastin time (APTT)
ANTICOAGULANTS:
• Levels of protein C increase from the second trimester
• Protein S fall as C4b binding protein increases.

#DAVIDSON_REVIEW
#HEMATOLOGY 4
Page 941-945
Iron deficiency anemia *****
Box 23.30 **********
Fig 23.18 **
Box 23.31 *****
Box 23.32 *****
Box 23.33 **********
Box 23.34 ***
Box 23.35 *
IRON DEFICIENCY ANEMIA
*** The most common explanation in men and post-menopausal women is
GASTROINTESTINAL BLOOD LOSS
** Worldwide, HOOKWORM (If SBA) and schistosomiasis are the most common causes of gut
blood loss
** Gastric acid is required to release iron from food and helps to keep iron in the soluble ferrous
state
*** Iron is absorbed actively in the UPPER SMALL INTESTINE (SBA)
and hence can be affected by coeliac disease
*** Serum ferritin is a measure of iron stores in tissues and is the best single test to CONFIRM
IRON DEFICIENCY (SBA)
** Ferritin levels can be raised in liver disease and in the acute phase response
** Plasma iron has a marked diurnal and day-to-day variation and becomes very low during an
acute phase response but is raised in liver disease and haemolysis.
*** Levels of transferrin, the binding protein for iron, are LOWERED BY MALNUTRITION,
LIVER DISEASE, THE ACUTE PHASE RESPONSE and NEPHROTIC SYNDROME, but
RAISED BY PREGNANCY AND THE ORAL CONTRACEPTIVE PILL
* All proliferating cells express membrane transferrin receptors to acquire iron
*** Indication of parenteral iron
• angina
• heart failure
• evidence of cerebral hypoxia
• Patients with malabsorption
• chronic gut disease
• inability to tolerate any oral preparation
FIG 23.18
*** Absorption Increased by
• Amino acids
• Vitamin C Dietary iron
*** Decreased by
• Phytates
• Tannins Phosphates
(আরও কিছু ফ্যাক্টর আছে physiology text/guide/sheet দেখে নিবেন)
** Source of iron / absorption
• 90% Non-haem iron / available for absorption < 5%
• < 10% Haem iron / available for absorption ~30%
*** Storage form
• Enzymes (2%)
• Myoglobin (4%)
• Ferritin (29%)
• Haemoglobin (65%) ( SBA)
Box 23.30
+ MCQ/SBA
(খুব খুব গুরুত্বপূর্ণ। বুঝে না পড়লে মনে থাকবে না)
ANEMIA OF CHRONIC DISEASE
** usually associated with a normal MCV (normocytic, normochromic), though this may be
reduced in long-standing inflammation.
*** The key regulatory protein that accounts for the findings characteristic of ACD/AI is
HEPCIDIN (SBA)
which is produced by the liver
*** Hepcidin production is induced by pro-inflammatory cytokines, especially IL-6 (SBA)
** A trial of oral iron can be given in difficult situations. A positive response occurs in true iron
deficiency but not in ACD
Box 23.31
+ MCQ
***
Most common : Malaise
Most common Neurological : Paraesthesia
Box 23.32
+ MCQ
(সব লাগবে কিন্তু)
*** Blood film,Reticulocytes,Bone marrow, Ferritin,LDH
BOX 23.33
+ SBA
+ Every point is important
*****
UMM lesion + Loss of vibration & proprioception + Loss of ankle reflex
MEGALOBLASTIC ANEMIA
* Folate is an important substrate of, and vitamin B12 a co-factor for, the generation of the
essential amino acid methionine from homocysteine
** Deficiency of either vitamin B12 or folate will therefore produce high plasma levels of
homocysteine and impaired DNA synthesis
** All proliferating cells will exhibit megaloblastosis; hence changes are evident in the buccal
mucosa, tongue, small intestine, cervix, vagina and uterus
*** Haemolysis within the marrow results in a raised bilirubin and lactate dehydrogenase
(LDH), but WITHOUT THE RETICULOCYTOSIS characteristic of other forms of haemolysis
** Iron stores are usually raised
*** Nuclear changes are seen in the immature granulocyte precursors and a
CHARACTERISTIC appearance is that of ‘GIANT’ METAMYELOCYTES with a large
‘SAUSAGE-SHAPED’ NUCLEUS. The mature neutrophils show HYPERSEGMENTATION
of their nuclei, with cells having six or more nuclear lobes (SBA)
*** The main pathological finding is focal demyelination affecting the SPINAL CORD,
PERIPHERAL NERVES, OPTIC NERVES AND CEREBRUM
*** The MOST COMMON MANIFESTATIONS are SENSORY, with peripheral paraesthesiae
and ataxia of gait (SBA)
*** FOR B12 Deficiency : Blood levels of vitamin B12 (cobalamin) - diagnostic of deficiency
and remain the first-line tests for most laboratories (SBA)
*** B12 absorption : in TERMINAL ILEUM by ACTIVE TRANSPORT (SBA)
* Spuriously low B12 values occur in women using the oral contraceptive pill and in patients
with myeloma
*** The finding of ANTI-INTRINSIC FACTOR ANTIBODIES in the context of B12 deficiency
is diagnostic of pernicious anaemia without further investigation (SBA)
* Antiparietal cell antibodies are present in over 90% of cases but are also present in 20% of
normal females over the age of 60 years
*** Pregnancy-induced folate deficiency is the most common cause of megaloblastosis
worldwide (SBA)
and is more likely in the context of twin pregnancies, multiparity and hyperemesis gravidarum
*** For folate deficiency : red cell folate levels are a more accurate indicator of folate stores and
tissue folate deficiency
(SBA)
* Serum folate measurement is very sensitive to dietary intake; a single folate-rich meal can
normalise it in a patient with true folate deficiency, whereas anorexia, alcohol and anticonvulsant
therapy can reduce it in the absence of megaloblastosis
*** The use of folic acid alone in the presence of vitamin B12 deficiency may result in
worsening of neurological features.
Box 23.34
+ MCQ
*** Drugs, Coeliac disease

#DAVIDSON_REVIEW
#HEMATOLOGY 7
(***** সম্ভবত Hematology এর সবচেয়ে গুরুত্বপূর্ণ টপিক গুলা এখানে আছে।প্রায় সব টপিক থেক scenario
based SBA আসার মত)
Page 966 - END
PARAPROTEINEMIA ***
MULTIPLE MYELOMA **********
FIG 23.31 **********
BOX 23.58 ***
BOX 23.61 ***
MYELOFIBROSIS ***
POLYCYTHEMIA RUBRA VERA *****
ITP *****
HEMOPHILIA **********
Fig 23.32 **
VWD *****
BOX 23.65 **
ANTIPHOSPHOLIPID SUNDROME ***
BOX 23.67 **********
DIC & BOX 23.68 (underlying condition) **********
TTP **********
PARAPROTEINEMIA
Polyclonal gammopathy
Acute or chronic inflammation, such as
• Infection
• Sarcoidosis
• Autoimmune disorders
• Some malignancies
Monoclonal proteins (also called M-proteins, paraproteins or monoclonal gammopathies)
• Myeloma,
• Lymphoma
• Amyloidosis
• Connective tissue disease such as rheumatoid arthritis or polymyalgia rheumatica
• Infection such as HIV
• Solid tumours
• In addition, they may be present with no underlying disease
** Gammopathies are detected by plasma immunoelectrophoresis.
MULTIPLE MYELOMA
*** Malignant proliferation of plasma cells
** Although a small number of malignant plasma cells are present in circulation, majority are
present in bone marrow
*** Male-to-female ratio of 2 : 1. The median age at diagnosis is 60–70 years
*** Dx criteria
+ increased malignant plasma cells in the bone marrow
+ serum and/or urinary M-protein
+ skeletal lytic lesions
*** Inv
+ Bone marrow aspiration
+ plasma and urine electrophoresis
+ skeletal survey
* Rx
+ High fluid intake to treat renal impairment and hypercalcaemia
+ Analgesia for bone pain.
+ Bisphosphonates for hypercalcaemia and to delay other skeletal related events
+ Allopurinol to prevent urate nephropathy
+ Plasmapheresis, if necessary, for hyperviscosity
*** Radiotherapy
+ localised bone pain not responding to simple analgesia and for pathological fractures (SBA)
+ emergency treatment of spinal cord compression complicating extradural plasmacytomas
*** poor prognostic features - a high β2-microglobulin and low albumin at diagnosis
FIG 23.31
+ সব পড়তে হবে
MOST IMPORTANT
*** Renal failure due to:
Paraprotein deposition
Hypercalcaemia
Infection
NSAIDs
Amyloid
*** Abnormal blood tests
Anaemia
Normo- or macrocytic
Pancytopenia
Raised ESR
Hypercalcaemia
Renal impairment
Paraproteinaemia
Immune paresis
*** Bone marrow
Plasmacytosis > 10%
*** Bence Jones proteinuria
Serum free light chains
BOX 23.58
*** MOST COMMON - Ig G (SBA)
Remember : Ig M ->>> Waldenström macroglobulinaemia
***** POSSIBLE SCENARIO
Middle/old age + Back pain + Renal impairment + Hypercalcemia >>> MM
APLASTIC ANAEMIA
*** Anaemia or bleeding, and less commonly, infections
*** An FBC demonstrates pancytopenia, low reticulocytes and often macrocytosis.
***** Possible scenario
Anemia + Bleeding manifestation + Pancytopenia + No organomegaly >>>> Aplastic anemia
MYELOPROLIFERATIVE NEOPLASM
*** Polycythemia rubra vera (PRV), essential thrombocythaemia and myelofibrosis are the non-
leukaemic myeloproliferative neoplasms
*** Mutation in the gene on CHROMOSOME 9 encoding the signal transduction MOLECULE
JAK-2 has been found in more than 90%
PRV cases and 50% of those with essential thrombocythaemia and myelofibrosis (SBA)
MYELOFIBROSIS
*** age of 50 years, with lassitude, weight loss and night sweats, spleen can be massively
enlarged
*** blood picture - LEUCOERYTHROBLASTIC anaemia, with circulating immature red blood
cells (increased reticulocytes and nucleated red blood cells) and granulocyte precursors
(myelocytes). The red cells are shaped like TEARDROPS (teardrop poikilocytes), and GIANT
PLATELETS may be seen in the blood. The white count varies from low to moderately high and
the platelet count may be high, normal or low. Urate levels may be high due to increased cell
breakdown, and folate deficiency is common.
*** Dx - TREPHINE BIOPSY shows an excess of megakaryocytes, increased reticulin and f
ibrous tissue replacement (SBA)
POLYCYTHAEMIA RUBRA VERA
*** Age of 40. Symptoms of hyperviscosity, such as lassitude, loss of concentration, headaches,
dizziness, blackouts, pruritus and epistaxis.Peptic ulceration is common. Patients are often
plethoric and many have a palpable spleen
** neutrophil and platelet counts are frequently raised
** Rx - Aspirin , Venesection
*** About 15% developing acute leukaemia or myelofibrosis
ITP
*** Autoantibodies, most often directed against the platelet membrane glycoprotein IIb/IIIa
(SBA)
*** associated with connective tissue diseases, HIV infection, B-cell malignancies, pregnancy
and certain drug therapies
** Spontaneous bleeding typically occurs only when the platelet count is below 20 × 109/L.
* At higher counts, the patient may complain of easy bruising or sometimes epistaxis or
menorrhagia
*** First-line therapy for patients with spontaneous bleeding is with high doses of
glucocorticoids (SBA)
* second-line therapies - thrombopoietin receptor agonists (TPO-RA), splenectomy and
immunosuppression
HAEMOPHILIA A
*** most common congenital coagulation factor deficiency (SBA)
*** Factor VIII is primarily synthesised by the liver and endothelial cells and has a half-life of
about 12 hours
*** It is protected from proteolysis in the circulation by binding to von Willebrand factor (vWF)
*** factor VIII gene is located on the X chromosome (SBA)
*** mutations include major inversions, large deletions and missense, nonsense and splice site
abnormalities
*** all daughters of a patient with haemophilia are obligate carriers
** Haemophilia ‘breeds true’ within a family; all members have the same factor VIII gene
mutation and a similarly severe or mild phenotype
* Female carriers of haemophilia may have reduced factor VIII levels because of random
inactivation of their normal X chromosome in the developing fetus
*** C/F (for SBA)
*** Spontaneous bleeding into skin, muscle and joints. Retroperitoneal and intracranial bleeding.
** major morbidity of recurrent bleeding is musculoskeletal
*** Bleeding is typically into large joints, especially knees, elbows, ankles and hips.
*** Muscle haematomas are also characteristic, most commonly in the calf and psoas muscles
* Recurrent bleeding into joints leads to synovial hypertrophy, destruction of the cartilage and
chronic haemophilic arthropathy
** A large psoas bleed - compress the femoral nerve; calf haematomas - compartment syndrome
with ischaemia, necrosis, fibrosis, and subsequent contraction and shortening of Achilles tendon
*** Rx - vasopressin receptor agonist desmopressin raises the vWF and factor VIII levels 3–4-
fold
*** Possible scenario
Joint/muscle swelling/hematoma following trauma +/- H/0 bleeding which took long time to stop
+ family history (maternal uncle)
>>> Hemophilia
BOX 23.62
*** SBA
+ Acquired factor X deficiency (in amyloid)
+ Acquired von Willebrand disease in Wilms’ tumour
+ Acquired factor VII deficiency in sepsis
VON WILLEBRAND DISEASE
*** quantitative (types 1 and 3) or qualitative (type 2) deficiency of von Willebrand factor
(vWF)
*** vWF -
+ synthesised by endothelial cells & megakaryocytes
+ Involved in both platelet function and coagulation
+ Acts as a carrier protein for factor VIII, to which it is non-covalently bound
+ bridges between platelets and subendothelial components (e.g. collagen),
+ deficiency of vWF therefore leads to impaired platelet plug formation
*** Blood group antigens (A and B) are expressed on vWF, reducing its susceptibility to
proteolysis; as a result, people with blood group O have lower circulating vWF levels than
individuals with non-O groups
*** Most patients with von Willebrand disease have a type 1 disorder (SBA)
** gene for vWF is located on chromosome 12 (SBA)
*** Disease is usually autosomal dominantly inherited, except in type 2N and type 3, where
inheritance is autosomal recessive
*** Superficial bruising, epistaxis, menorrhagia and gastrointestinal haemorrhage are common
** Within a single family, the disease has variable penetrance, so that some members may have
quite severe and frequent bleeds, whereas others are relatively asymptomatic
*** patients with type 2B disease develop thrombocytopenia
***** Remember usually
In hemophilia - deep tissue bleeding
In vWD - Superficial bleeding
ANTIPHOSPHOLIPID SYNDROME
* APS may present in isolation (primary APS) or in association most typically systemic lupus
erythematosus (secondary APS)
*** Arterial thrombosis, typically stroke, associated with APS should probably be treated with
warfarin, as opposed to aspirin.
Box 23.67
+ কোন কিছু বাদ দেওয়া যাবে না।
DISSEMINATED INTRAVASCULAR COAGULATION
*** Simultaneous coagulation factor and platelet consumption, causing bleeding
*** Consumption of platelets, coagulation factors (notably factors V and VIII) and fibrinogen
** frozen plasma, cryoprecipitate and platelets, should be given
*** Patients with DIC should not, in general, be treated with antifibrinolytic therapy, e.g.
tranexamic acid
*** Thrombosis with paradoxical thrombocytopenia
+ DIC
+ Heparin-induced thrombocytopenia
+ Thrombotic thrombocytopenic purpura (TTP)
TTP
*** PENTAD (FOR SBA)
• Thrombocytopenia
• microangiopathic haemolytic anaemia
• neurological sequelae
• fever
• renal impairment
*** antibodies against ADAMTS-13 (SBA)
*** association with drugs (ticlopidine, ciclosporin), HIV, shiga toxins and malignancy
*** Rx - emergency plasma exchange.
*** Remember :
In HUS - Renal involvement is more
In TTP - Brain involvement is more
********* For SBA
+ Clinical features of MULTIPLE MYELOMA, PRV, ITP, HEMOPHILIA, vWD, DIC, TTP
+ Blood picture of MM, PRV, ITP
+ Findings (ex- BT,CT,PT,APTT etc.) of HEMOPHILIA,vWD,DIC
(In sha ALLAH i will try to give a post regarding this. But before that read from a guide or
sheet)
End of HEMATOLOGY..

#DAVIDSON_REVIEW
#HEMATOLOGY 6
PAGE : 950-965
Fig 23.22 *****
Sickle cell anemia ***
Thalassemia **********
Box 24.40 *****
Box 23.44 ***
Box 23.48 ***
Box 23.49 **
CML **********
CLL ***
BOX 23.51 **
Hodgkin's lymphoma *****
Fig 23.25 **
Box 23.53 *
Box 23.54 ***
Box 23.56 *****
Box 23.57 **
HEMOGLOBINOPATHIES
* Alpha globin chains are produced throughout life, including in the fetus, so severe mutations
may cause intrauterine death.
* Disorders affecting the beta chains do not present until after 6 months of age.
** Qualitative abnormalities – abnormal haemoglobins : example is haemoglobin S, found in
sickle-cell anaemia
** Quantitative abnormalities – thalassaemias.
* In alpha-thalassaemia excess beta chains are present, while in beta-thalassaemia excess alpha
chains are present
* The excess chains precipitate, causing red cell membrane damage and reduced red cell survival
due to haemolysis.
SICKLE-CELL ANAEMIA
*** Results from a single glutamic acid to valine substitution at position 6 of the beta globin
polypeptide chain (SBA)
*** autosomal recessive trait
** Individuals with sickle-cell trait are relatively resistant to the lethal effects of falciparum
malaria
***** CLINICAL FEATURES / FIG 23.22
** Sickling is precipitated by hypoxia, acidosis, dehydration and infection.
*** Painful vaso-occlusive crisis - most common form of crisis (SBA)
*** Stroke - single most devastating consequence of sickle-cell disease (SBA)
*** Sickle chest syndrome - most common cause of death in adult sickle-cell disease (SBA)
* Aplastic crisis - Infection of adult sicklers with human parvovirus B19 (erythrovirus)
** Blood film shows sickle cells, target cells and features of hyposplenism. A reticulocytosis is
present
*** Definitive diagnosis - haemoglobin electrophoresis (absence of HbA, 2–20% HbF and the
predominance of HbS) (SBA)
* All patients with sickle-cell disease should receive prophylaxis with daily folic acid
THALASSEMIA
*** In alpha-thalassaemia.- chromosome 16 *** In betathalassaemia - point mutation
*** beta-thalassaemia is the most common type of thalassaemia
HEMATOLOGICAL MALIGNACY
*** Haematological neoplasms are diseases of elderly patients, the exceptions being acute
lymphoblastic leukaemia, which predominantly affects children, and Hodgkin lymphoma, which
affects people aged 20–40 years
* Acute lymphoblastic leukaemia shows a peak of incidence in children aged 1–5 years
BOX 23.44
+ MCQ
IMPORTANT
+ Name/headlines
*** X-ray, Benzene,HTLV-1,Downs syndrome, Hypogammaglobulinmaemia
Acute leukemia
*** Investigation findings
*** The presence of Auer rods in the cytoplasm of blast cells indicates a myeloblastic type
Box 23.48
+ MCQ
+ Only name of risk factors
CHRONIC MYELOID LEUKEMIA
+ Scenario based SBA
+ Clinical features, Investigation ***** (সব features ভাল করে পড়তে হবে)
*** Defining characteristic of CML is the chromosome abnormality known as the Philadelphia
(Ph) chromosome (SBA)
*** This is a shortened chromosome 22 resulting from a reciprocal translocation of material with
chromosome 9
*** BCR ABL fusion gene codes for a protein with tyrosine kinase activity
* Chronic phase - responsive to treatment and is easily controlled, which used to last 3–5 years
* An accelerated phase (not always seen) - disease control becomes more difficult
* Blast crisis - disease transforms into an acute leukaemia, either myeloblastic (70%) or
lymphoblastic (30%), which is relatively refractory to treatment. This is the cause of death in the
majority of patients
C/F
* lethargy, weight loss, abdominal discomfort, gout and sweating
*** Splenomegaly , Hepatomegaly . Lymphadenopathy is unusual
*** In the blood film, the full range of granulocyte precursors, from myeloblasts to mature
neutrophils, is seen but the PREDOMINANT CELLS ARE NEUTROPHILS AND
MYELOCYTES
* Myeloblasts usually constitute less than 10% of all white cells
*** Bone marrow should be obtained to confirm the diagnosis
** ↑LDH, ↑uric acid
*** PBF findings,Bone marrow findings ( ব গুলো পয়েন্ট পড়তে হবে।দরকার হলে শীট বা গাইড দেখে
নিবেন)
BOX 24.49
+ First line drugs
CLL
*** This the most common variety of leukaemia, accounting for 30% of cases (SBA)
** Myelodysplastic syndromes - ineffective blood cell production and a tendency to progress to
AML. Pre-leukaemic and represent genetic steps in the development of leukaemia
LYMPHOMA
Fig. 23.25
*** B cells in the follicles, T cells in the paracortex and plasma cells in the medulla
*** Majority are of B-cell origin.
HODGKIN'S LYMPHOMA
*** The histological hallmark of Hodgkin lymphoma (HL) is the presence of Reed–Sternberg
cells: large, malignant lymphoid cells of B-cell origin (SBA)
* Surrounded by large numbers of reactive non-malignant T cells, plasma cells and eosinophils
*** Nodular sclerosing type is more common in young patients and in women. Mixed cellularity
is more common in the elderly (SBA)
***** Clinical features
*** Painless, rubbery lymphadenopathy, usually in the neck or supraclavicular fossae;
** Hepatosplenomegaly may be present
***POOR PROGNOSTIC FACTORS
• Normochromic, normocytic anaemia or
• lymphopenia
• ↑LDH
• Bulky disease (> 10 cm in a single node mass)
•
** Positron emission tomography (PET) scanning allows more accurate staging and monitoring
of response
** Prognosis - Over 90% of patients with early-stage HL achieve complete remission & the great
majority are cured.
Box 23.56
+ Only name of risk factors
NON-HODGKIN LYMPHOMA
** B-cell (90%) or T-cell (10%) origin
** High-grade NHL
• high proliferation rates
• rapidly produces symptoms
• fatal if untreated
• but is potentially curable
** Low-grade NHL
• low proliferation rates
• may be asymptomatic for many months or even years before presentation
• runs an indolent course
• but is not curable by conventional therapy
CLINICAL FEATURES
** Unlike Hodgkin lymphoma, NHL is often widely disseminated at presentation, including in
extranodal sites
** Patients present with lymph node enlargement which may be associated with systemic upset:
weight loss, sweats, fever and itching
** Hepatosplenomegaly may be present.
* Sites of extranodal involvement include the bone marrow, gut, thyroid, lung, skin, testis, brain
and, more rarely, bone
* Bone marrow involvement is more common in low-grade (50–60%) than high-grade (10%)
disease
* Compression syndromes may occur, including gut obstruction, ascites, superior vena cava
obstruction and spinal cord compression
(TB & Lymphoma এর clinical presentation very similar. So be careful..)
Box 23.57
*** Median age 65–70 years
*** EBV - post-transplant NHL, HHV8 - primary effusion lymphoma, and
HTLV-1 - adult T-cell leukaemia lymphoma •
*** Gastric lymphoma - Helicobacter pylori infection
** Lymphoma occurs in congenital immunodeficiency states and in immunosuppressed patients
after organ transplantation

#DAVIDSON_REVIEW
#HEMAT0LOGY 5
PAGE 946-950
FIG 23.19 **********
BOX 23.36 ***********
Fig 23.20 *****
BOX 23.37 ***
Box 23.38 ***
Hereditary spherocytosis ***
Hereditary eliptocytosis **
G6PDD ***
Autoimmune hemolytic anemia *****
PNH ***
Fig 23.19
+ SBA/MCQ
Q: Inherited Causes of hemolytic anemia (HA)?
Q: In which conditions coombs test / direct coombs test is positive?
Ans : All immune causes of this figure
Q: Warm or cold Ab found in?
Q: Causes of non -immune HA/Mechanical causes of HA?
Q: Malignancy/Infection/Connective tissue disease causing HA?
SBA: Acquired Abnormal membrane defect causing HA?
SBA scenario: Liver disease/Parkinson like feature + HA > Wilson disease
Box 23.36
+ MCQ/SBA
*** Hallmarks
All ↑except Hb & haptoglobin
Fig 23.20
+ MCQ
See fig 23.19 for causes of AIHA
BOX 23.37
*** Pneumococcal, Haemophilus influenzae type B, meningococcal group C and influenza
vaccines at least 2–3 weeks before elective splenectomy
* Pneumococcal re-immunisation should be given at least 5-yearly and influenza annually
*** Life-long prophylactic penicillin V
Box 23.38
*** Name of drugs
*** PBF finding
HEMOLYTIC ANEMIA
* Bone marrow may increase its output of red cells six- to eightfold
** Increased proliferation of the bone marrow can result in a THROMBOCYTOSIS,
NEUTROPHILIA and, if marked, immature granulocytes in the blood, producing a
LEUCOERYTHROBLASTIC blood film
*** Spherocytes are small, dark red cells - autoimmune haemolysis or hereditary spherocytosis
** Bite cells suggest oxidative haemolysis.
EXTRAVASCULAR HAEMOLYSIS
*** Site : Reticulo-endothelial cells in the liver or spleenIn
*** Most haemolytic states, haemolysis is predominantly extravascular
Examples (Fig 23.19 not mentioned in book)
• Hb Abnormalities
• RBC membrane defect
• Warm Ab
• Hemolytic disease of newborn
INTRAVASCULAR HEMOLYSIS
EXAMPLES
• RBC enzymes Defects
• Cold Ab
• Transfusion reaction
• Non immune causes
*** Haemosiderinuria is always indicative of intravascular haemolysis
HEREDITARY SPHEROCYTOSIS
*** autosomal dominant
*** The most common abnormalities are deficiencies of BETA SPECTRIN OR ANKYRIN
(SBA)
* Pigment gallstones are present in up to 50% of patients and may cause symptomatic
cholecystitis
***
• A haemolytic crisis associated with infection
• A megaloblastic crisis in pregnancy
• An aplastic crisis with parvovirus (erythrovirus) infection
INVESTIGATION
** Direct Coombs test is negative. Osmotic fragility test may show increased sensitivity to lysis
in hypotonic saline solutions
*** SBA: More specific flow cytometric tests
*** Scenario
Family history + Right upper quadrant abdominal pain (gallstones) + HA >>> Think Hereditary
spherocytosis
HEREDITARY ELLIPTOCYTOSIS
*** Autosomal dominant or recessive.
*** abnormality of alpha spectrin or protein 4.1
RED CELL ENZYMOPATHIES
*** ATP is generated by glycolysis & defect in GLYCOLYSIS pathway result in shortened red
cell survival & CHRONIC HAEMOLYSIS
*** Hexose monophosphate shunt produces nicotinamide adenine dinucleotide phosphate
(NADPH) & glutathione to protect against oxidative stress & DEFECTS IN HMP shunt pathway
result in PERIODIC HAEMOLYSIS precipitated by episodic oxidative stress
GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
*** G6PD is pivotal in the hexose monophosphate shunt pathway.
*** Most common human enzymopathy (SBA)
*** encoded by a gene on the X chromosome
PYRUVATE KINASE DEFICIENCY
* Second most common red cell enzyme defect
* results in deficiency of ATP production and a chronic haemolytic anaemia
*** autosomal recessive trait
** blood film shows characteristic ‘prickle cells’ that resemble holly leaves
PYRIMIDINE 5′ NUCLEOTIDASE deficiency
** important during the degradation of RNA in reticulocytes
*** autosomal recessive trait
*** accumulation of excess ribonucleoprotein results in coarse BASOPHILIC STIPPLING
*** The enzyme is very sensitive to inhibition by lead and this is the reason why basophilic
stippling is a feature of lead poisoning.
AUTOIMMUNE HAEMOLYTIC ANAEMIA
** Antibodies may be IgG or IgM, or more rarely IgE or IgA
*** WARM ANTIBODIES
• bind best at 37°C
• account for 80% of cases
• Majority are IgG
• Often react against Rhesus antigens
*** Cold antibodies
• bind best at 4°C but can bind up to 37°C in some cases
• Usually IgM & bind complement
• 20% of cases
* Direct Coombs test can be negative in the presence of brisk haemolysis
* A positive test requires about 200 antibody molecules to attach to each red cell; with a very
avid complement-fixing antibody, haemolysis may occur at lower levels of antibody-binding
** The standard Coombs reagent will miss IgA or IgE antibodies
* Around 10% of all warm autoimmune haemolytic anaemias are Coombs test-negative
*** MICROANGIOPATHIC HAEMOLYTIC ANAEMIA
• disseminated carcinomatosis,
• malignant or pregnancy-induced hypertension
• haemolytic uraemic syndrome
• thrombotic thrombocytopenic purpura
• disseminated intravascular coagulation
PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA
*** ACQUIRED, NON-MALIGNANT clonal expansion of haematopoietic stem cells deficient
in glycosylphosphatidylinositol (GPI) anchor protein (CD55 and CD59)
(SBA)
*** Episodes of intravascular haemolysis result in haemoglobinuria, most noticeable in early
morning urine, which has a characteristic red–brown colour (SBA SCENARIO)
*** Associated with an increased risk of venous and arterial thrombosis in unusual sites, such as
the liver or abdomen
*** PNH clones are also associated with hypoplastic bone marrow failure, aplastic anaemia and
myelodysplastic syndrome
*** Standard care now includes the anti-complement C5 monoclonal antibody eculizimab (SBA)
*** Eculizumab carries a risk of infection, particularly for Neisseria meningitidis, and all treated
patients must be vaccinated against this organism