Hematology notes

1. Board Review - Hematology
E. E. Okon MRCS

2. Hemostasis

Definition:
 Sequence of events
 Formation of a stable fibrin-platelet hemostatic plug

Interactions
 Vascular wall
 Platelets
 Coagulation system

3. Vascular Wall Injury

Thrombogenic vs Anti-thrombogenic factors

Initiate the process of formation of platelet plug

Thrombogenic
 Endothelin-1
 Tissue Factor ( factor II- extrinsic Pathway)
 Collagen & Factor XII (Intrinsic Coagulation
Pathway)
 Von Willebrand factor (vWF)

Anti-thrombogenic Factors
 Prostacyclin – Prevents Platelet aggregation
 Nitric oxide
 TPA
 Thrombomodulin

4. Platelets

Facilitates formation of a platelet plug

Adhesion, Aggregation, and Platelet swelling

Alpha Granules
Dense Bodies

• Fibrinogen • ADP (potent platelet aggregator)

• Fibronectin • Calcium

• Factor V and vWF • Histamine and serotonin

• Platelet factor 4 • Epinephrine

• Platelet-derived growth factor (PDGF)

6. Platelet Adhesion

Collagen

von Willebrand factor (Platelets & Endothelium)

Glycoprotein Ib (GpIb) receptor

Stabilizer for Factor VIII

7. Von Willebrand Factor
● Quantitative (types 1 and 3) and qualitative
(types 2A, 2B, 2M, and 2N) abnormalities of
vWF result in vWD.
● The 2 main functions of vWF are
– 1) to mediate platelet adhesion and aggregation
and
– 2) to act as a carrier protein for factor VIII,
protecting it from proteolytic inactivation

8. Disorders of Platelet Adhesion

Von Willebrand disease
 Autosomal dominant
 Spontaneous bleeding from mucous membranes, prolonged
bleeding from wounds, and menorrhagia in young females.
 Bleeding may be exacerbated by aspirin or NSAID use
 Hemarthrosis is uncommon.
Lab studies: Type 1 - a mild to moderate reduction in vWF
antigen (vWF:Ag) and activity
Type 3 - vWF is absent.
Healthy people with blood group O have vWF levels that are 25%
to 30% lower than in people with blood groups A, B or AB; thus,
they may receive a misdiagnosis of vWD. Therefore, ABO typing
should be part of the initial testing.
 Normal platelet count, Normal PT,
 Prolonged PTT, Prolonged bleeding time

9. Diagnostic: Abnormal platelet response to ristocetin
Normalizes after addition of normal plasma
Treatment: Desmopressin (ADH Analog)
Intravenous infusion of 0.3 mcg/kg body weight releases vWF
from its storage sites; levels should be measured 60 minutes after infusion.
Side effects include facial flushing, headache, mild decrease in blood pressure,
mild tachycardia, and hyponatremia. Repeated doses at intervals shorter than 24
hours may result in a decrease or loss of response (tachyphylaxis) and syndrome
of inappropriate antidiuresis (SIAD), leading to hyponatremia and seizures.
Type 3 vWF: purified plasma-derived vWF concentrates are the therapy of
choice

10. 
Bernard-Soulier syndrome
 Autosomal recessive
 Lack of GpIb receptor.
 Labs: Prolonged Bleeding Time, Thrombocytopenia
 Abnormal ristocetin cofactor assay

Not correctable with normal plasma infusion

11. Platelet Aggregation

ADP and Thromboxane A2

Insertion of glycoprotein IIb/IIIa (GpIIb/GpIIIa)
receptors on the platelet surface.

Platelets bind to each other by binding to
fibrinogen using GPIIb-IIIa

12. Disorders of Platelet Aggregation

Uremia or Renal Failure
 Accumulation of toxic products
 Inhibition of platelet phospholipids
 Prolonged Bleeding Time
 Treatment: Dialysis & Desmopressin acetate

Glanzmann disease
 Autosomal recessive
 Gp IIb/IIIa receptor deficiency
 Prolonged BT

13. Coagulation Cascade

Two Pathways
 Extrinsic Pathway – Defect in PT
 Intrinsic Pathway – Defect in PTT (25 to 40
seconds)
 Activation of Factor II to IIa and Fibrinogen to Fibrin

Extrinsic Pathway
 Trauma to the endothelium
 Tissue Factor (factor III) and tissue phospholipids.
 TF-FVII complex

Co-factors: Vitamin K, Calcium

15. 
Intrinsic Pathway
 Activation of Factor XII
 Collagen

Key Points:
 Vitamin K dependent factors: II, VII, IX, X, Protein C
& S
 All Vitamin K dependent factors require Calcium
 Clinical: Neonates require Vitamin K
 Constant activation of the coagulation system leads
to deficiency in I, II, V and VIII. (sepsis, DIC)

16. Anticoagulant System

Regulate clot formation

Two systems
 Protein C & S

Vit. K dependent

Protein C activated by thrombomodulin.

Inactivates Factors Va, VIIIa

Protein S – cofactor for activated Protein C
 Antithrombin

Serine protease inhibitor

Inhibits Factors Iia, VIIa, Ixa, Xa, Xia, Xiia

Heparin*

17. Pathology

RBC pathology: Anemia
 Definition:
 Symptoms and Signs
 *Underlying Disease not a diagnosis*
 Abnormal Shapes and sizes (Poikilo-; Aniso-;)

Spherocytes

Elliptocytes

Target cells

Acanthocytes

Echinocytes

Schistocytes

Bite cells

Teardrop cells

Sickle cells


18. Lab Report of CBC

Hb – Concentration of Hb in the blood

Hct – Percentage Value of volume of RBCs in
the blood

MCV - average RBC volume; normal range is
80 to 100 fL

RDW - measure of the variation in width of
RBCs

MCHC – average concentration of Hb in RBCs.

Reticulocyte count - decreased RBC
production or decreased survival of RBCs

Corrected reticulocyte count = (measured
Hct/45) × reticulocyte count.

19. Approach to Anemia

Determine whether patient is anemic by looking
at the Hb.

Classify the anemia as microcytic, normocytic,
or macrocytic by looking at the MCV.

Determine whether the bone marrow is
compensating appropriately by looking at the
reticulocyte count (use correction formulas if
necessary).

20. 
Classification of Anemia can be based on
 Colour
 Size

22. 
Immune hemolytic Anemia
 AIHA
 HDN

Hemolytic Anemias
 G6PD
 Sickle Cell
 Pyruvate Kinase Deficiency
 PNH

23. Microcytic Anemia

Acquired – Iron Deficiency Anemia

Functional Iron – Hemoglobin, myoglobin,
Catalase and Cytochrome

Ferritin

Hemosiderin

Ferroportin
 inhibited by hepcidin
 Retention of Iron inside cells

Transferrin
 TIBC – 300microgm/L
 Saturation – 33%

24. 
Iron Deficiency Anemia

Dietary deficiency - elderly populations,
children,poor, pregnant women

Decreased absorption

Generalized malabsorption

Post-gastrectomy

Chronic Blood loss


25. Stages of IDA

Decreased storage iron leading to Decreased
serum ferritin.

Decreased circulating iron.

Formation of microcytic/hypochromic anemia.

26. Pathophysiology of IDA

Clinical signs of IDA include the following:

Pallor, fatigue, shortness of breath

Glossitis—inflammation of the tongue

Koilonychia—concave or spoon-shaped nails

Pica—obsessive craving for nonnutritional
materials (e.g., ice, dirt)
 Plummer Vinson Syndrome

29. Laboratory

Increased RDW

Hb, Hct, and MCV are decreased

Serum iron and Ferritin levels will be decreased

Iron saturation will be decreased

TIBC will be increased

Increased free erythrocyte protoporphyrin
(FEP)

30. Treatment

Oral iron supplementation

Supplementation with vitamin C

31. Anemia of Chronic Disease

Iron being trapped in bone marrow
macrophages

Most common anemia in hospitalized patients

Chronic illness leads to continued released of
cytokines (Il-6)

IL-6 signals the liver to release Hepcidin

Increased retention of iron in cells

32. Common causes

Chronic Infectious Diseases - ???

Chronic non-infectious inflammatory diseases
- ???

Neoplasms - ???

33. Diagnosis

Decreased Hb (rarely < 9 g/dL), Hct, and MCV.

Increased ferritin

Decreased serum iron, TIBC, and iron
saturation – Why?

Transferrin – low or normal


34. Treatment

Treat the underlying condition

Administration of erythropoietin