HAEM - bleeding disorders

Question 1

What does Activated Partial thromboplastin time (APTT) measure?

Answer 1

Intrinsic pathway coagulation (factors 8, 9, 11, 12)

Surface activating agent (Ellagic acid, kaolin)
Phospholipid
Calcium

Question 2

What does Prothrombin time (PT) measure?

Answer 2

Extrinsic pathway (factor 7)

(remember PT is used for INR and INR is related to vitamin K & warfarin. Vitamin K helps produce factors 2, 7, 9, 10, and factor 7 is uniquely in EXTRINSIC - hence it measures extrinsic pathway)

Question 3

What does Thrombin time measure?

Answer 3

Common pathway

Question 4

(4) features of screening tests for hemostatic defects

Answer 4

• Platelet Count (150 - 400)
• Activated Partial Thromboplastin Time (Aptt) (24-32 Seconds)
• Prothrombin Time(pt)(10 -12 Seconds)
• Thrombin Time

Question 5

How can you differentiate factor deficiency from presence of ‘inhibitor’ in coagulation?

Answer 5

Perform Mixing study:
Mix 1/2Pt + 1/2 Control (CONTROL - POOLED PLASMA from normal individuals) and perform APTT or PT

• If factor deficiency = APTT / PT will normalize (the control pool will make up for the deficiency)
• If ‘inhibitor’present = persistent abnormality (inhibitor will affect the control pool also)

Question 6

(3) Causes of corrected APTT after Mixing study in previously normal PT, prolonged APTT

Answer 6

• Factor deficiency (VIII, IX, XI, XII)
• Early DIC
• Heparin Rx (variable correction)

Question 7

(2) Causes of persistent abnormality after Mixing study in previously normal PT, prolonged APTT

Answer 7

• Lupus anticoagulant (common)

- Inhibitors towards specific coagulant factors VIII, IX, XI

Question 8

(3) Causes of corrected PT after Mixing study in previously prolonged PT, normal APTT

Answer 8

• Factor deficiency (VII)-rare
• Liver disease, Vit K defi
• Warfain (above are common)

Question 9

(2) Causes of persistent abnormality after Mixing study in previously prolonged PT, normal APTT

Answer 9

• Antiphospholipid ab’s: uncommon

- Antibodies to VII: rare

Question 10

(2) Causes of corrected PT/APTT after Mixing study in previously prolonged PT, prolonged APTT

Answer 10

• Isolated deficiency in common pathway: Factors V, X, II, and fibrinogen
• Multiple factor deficiencies (common): Liver disease, vitamin K deficiency, warfarin, DIC

Question 11

(3) Causes of persistent abnormality after Mixing study in previously prolonged PT, prolonged APTT

Answer 11

• Inhibitors towards V, X, II
• fibrinogen (rare)
• anti-phospholipid ab’s

Question 12

(5) causes of prolonged PT

Answer 12

• Warfarin (F II, VII, IX, X)
• Liver disease
• Vitamin K deficiency
• DIC
• Factor VII deficiency

Question 13

(7) causes of prolonged APTT

Answer 13

• Heparin anticoagulation therapy
• Liver disease
• Lupus anticoagulant
• DIC
• von Willebrand’s disease
• Haemophilia: Factor VIII, Factor IX deficiency
• Factor XII, XI deficiency

Question 14

(3) causes of prolonged thrombin time (TT)

Answer 14

• DIC (decreased fibringogen)
• Liver disease
• Heparin

Question 15

Describe purpuric disorders

• petechiae
• superficial echymoses
• haematoma & haemarthrosis
• late bleed
• gender
• FMHx

Answer 15

Purpuric disorders have characteristic petechiae, small & multiple superficial echmoses

• rare haematoma, haemarthrosis
• rare late bleed
• females > males
• variable FMHx

Question 16

Describe coagulation disorders

• petechiae
• superficial echymoses
• haematoma & haemarthrosis
• late bleed
• gender
• FMHx

Answer 16

Coagulation disorders have rare petechiae, large & solitary superficial echymoses

• characteristic haematoma & haemarthrosis
• common late bleed
• 80-90% males
• common FMHx

Question 17

(4) Common hereditary bleeding disorders

Answer 17

• Hemophilia – A /B
• Von Willebrand disease
• Factor deficiency
• Platelet Disorders

Question 18

(5) common acquired bleeding disorders

Answer 18

–Liver disease
–Vit K deficiency
–DIC
–Excessive anticoagulation
–ITP (idiopathic thrombocytopaenic purpura)

Question 19

(2) functions of vWF

Answer 19

1. vWF mediates platelet adhesion at site of injury
2. Stabilizes FVIII in circulation

Remember: Wherever platelet aggregation is needed, coagulation is also necessary. vWF is like a ‘taxi’ that carries fVIII to the proximity of a developing clot

Question 20

What modifies penetrance of type I von Willebrand disease?

Answer 20

ABO group

• ABO glycosylation of vWF influences clearance
• People with non-O blood group have higher levels compared with O-group
• Blood group AB people have highest level

Question 21

Describe type 1, 2, 3 of von Willebrand’s disease

Answer 21

Type 1 -partial quantitative deficiency of VWF
–70-80% cases- Ad
–Mild presentation / blood group.

Type 2 -qualitative deficiency of VWF

• Subtypes : Differences in multimers
• Mild to moderate bleeding.
• Abnormal Multimers

Type 3- virtually complete deficiency of VWF

All have prolonged APTT

Question 22

Specific Ix for vWD (von Willebrand’s disease)

Answer 22

• von Willebrand Factor Antigen (vWAg)
• Factor VIII clotting activity : VIII C
• Functional assays : Ristocetin Co-Factor activity/Collagen-binding assay

Question 23

Rx for vWD

Answer 23

• Desmopressin (DDAVP): Releasing FVIII & vWFAg from storage sites. Effective in Type 1.
• Replacement Therapy
• Antifibrinolytics - Tranexamic acid
• Fibrin Glue / Fibrillar collagen preparation

Question 24

Explain pathophysiology of haemophilia A

• factors involved
• genetics

Answer 24

–Factor VIII deficiency
–F VIII normally circulates bound to vWf, which protects F VIII from proteolysis

Genetics:
–X-linked recessive (gene on X chromosome)
–Males present with features of disease (males = XY)

Question 25

Clinical Px of haemophilia A

Answer 25

–Hemarthrosis –Subcutaneous and intramuscular haematomas –Psoas and retroperitoneal haematomas –Traumatic bleeding: •Bleeding from razor nicks is uncommon •Delayed bleeding is common especially in tooth extractions, tonsillectomy •Wound healing is slow in haemophiliacs

Question 26

Which clotting profile would be abnormal in haeomphilia A?

Answer 26

APTT (factor 8 deficient) INR is normal

Question 27

Rx of haemophilia A

Answer 27

–Purified or Recombinant F VIII therapy –Tranexamic acid –Topical thrombin –Role of FFP

Question 28

Describe haemophilia B - factor involved - prevalance compared to haem A - genetic

Answer 28

* Factor IX deficiency * 4-8 times less common than Haemophilia A * X-linked recessive * Unlike Haemophilia A, spontaneous mutation rate is low, most patients have family history * Severe disease manifests identical to Haemophilia A

Question 29

Which factor is deficient in haemophilia A?

Answer 29

Factor 8

Question 30

Which factor is deficient in haemophilia B?

Answer 30

Factor 9

Question 31

Ix of haemophilia B

Answer 31

–Prolonged APTT (factor 9 deficiency), Normal INR | –APTT not sensitive to mild deficiency (F IX 20-30%)

Question 32

Rx of haemophilia B

Answer 32

–Prothrombin complex | –Purified or Recombinant F IX

Question 33

What is thrombocytopaenia?

Answer 33

deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury

Question 34

What are the causes of thrombocytopaenia? - increased destruction - decreased production

Answer 34

Increased destruction 1. Auto-Immune: - ITP - SLE etc - Drugs 2. Allo-immune: - Post Transfusion Purpura - Neonatal Allo-Immune Thrombocytopenia 3. Non-immune: - Hypersplenism - DIC / TTP / HUS Decreased production - Aplastic Anaemia - Myelodysplasia - Leukaemic infiltration - Lymphoma infiltration - Fibrosis

Question 35

Where do you typically bleed in thrombocytopaenia?

Answer 35

``` •Skin and mucous membranes –Petechiae –Ecchymosis –Hemorrhagic vesicles –Gingival bleeding and epistaxis ``` * Menorrhagia * Gastrointestinal bleeding * Intracranial bleeding

Question 36

(4) How do you assess the function of platelets?

Answer 36

1. Thromboelastography (TEG) 2. PLATELET AGGREGATION STUDIES - ADP - COLLAGEN - ADRENALINE - RISTOCETIN 3. Plt Function Analysis (PFA) 4. Skin Bleeding Time: No longer preferred as technical issues of standardization and expertise