5. Haemorrhagic Disorders

Question 1

What are vascular bleeding disorders?

Answer 1

• characterised by easy bruising and spontaneous bleeding from small vessels
• mainly in skin
• abnormality in the vessel or in perivascualr connective tissue
• not usually severe bleeding

Question 2

What are some different types of vascular bleeding disorders?

Answer 2

Inherited
- Hereditary haemorrhagic telangiectasia (HHT)
— AD
— Dilated microvascular swellings increase in number with age in the skin, mucous membranes, GIT, lungs and CNS

Acquired

• common
• Senile purpura
• Purpura associated with infection due to vascular damage or organism/immune complex formation eg measles, dengue, meningococcal sepsis
• Henoch-Schonlein syndrome
• Scurvy
• Steroid purpura
• Connective tissue disorders

Question 3

What are the different classifications of skin bleeds?

Answer 3

• Petechia - less than 3mm
• Pupura - between 3mm and 1cm
• Ecchymoses - greater than 1cm

Question 4

What are the different types of platelet disorders?

Answer 4

Quantitative

• thrombocytopenia - decreased platelets
• thrombocytosis - increased
• can be due to too much/ too little TPO

Qualitative

• Acquired - drugs eg aspirin, clopidogrel; plus liver/renal failure
• Hereditary - rare eg Glanzmann disease (absent GPIIb/IIIa), Bernard-Soulier disease (absent GP1b)

Question 5

What is idiopathic thrombocytopenic purpura?

Answer 5

• AI disease
• diagnosis based on exclusion of other causes eg. Alcohol, drugs, liver disease, infection
• antiplatelet autoantibodies lead to reduced survival and removal of platelets by RES (spleen and liver)

Labs

• low platelets usually 10-50 (nr 150-400)
• Hb and WCC normal
• Large platelets on blood film, and megakaryocytes on BM biopsy
• Normal PT and AAPTT

Tx

• emergency - corticosteroids, IV Abs and tranexamic acid (antifibrinolytic)
• Second line - TPO receptor agonists, immunosuppressants
• Splenectomy

Question 6

What is DIC?

Answer 6

• pathological activation of the cascade
• widespread microthrombi -> ischaemia and infarction -> multi-organ failure
• leads to consumption of platelets and factors I, II, V, VII
• lose haemostatic control
• almost always secondary to another disease

Lab

• low platelets, prolonged PT and APTT
• low fibrinogen, high d-dimer

Tx

• Treat underlying cause
• resuscitation
• blood product replacement - red cells, platelets, FFP, cryoprecipitate

Question 7

How does warfarin work?

Answer 7

• Vitamin K anatgonist
• Vit K is activated by epoxide reductase in the liver (warfarin’s target)
• Vit K is needed to activate factors II, VII, IX and X
• has a narrow therapeutic window
• need to monitor carefully
• PT —> INR

Question 8

How does liver failure affect clotting?

Answer 8

May cause bleeding OR thrombosis

• Decreased production of coag factors
• Decreased activation of vit k by epoxide reductase (takes place in liver)
• Decreased synthesis of fibrinolytic agents (plasminogen)
• Also decreased synthesis of ATIII, protein C and S
• Decreased clearance of fibrinogen and split products

Both the PT and APTT may be abnormal, but PT of greater use

Question 9

What disorders can we get of fibrinolysis?

Answer 9

• plasmin overactivity
• plasmin cleaves fibrin and fibrinogen to fibrinogen degradation products (FDPs) - d-dimer
• blocks lateral aggregation
• Radical prostatectomy-> releases urokinase, activates plasminogen
• Liver cirrhosis -> decreased a2-antiplasmin -> less plasmin inactivation
• presents with bleeding, looks like DIC
• FDP - can interfere with platelet activation, so bleeding time is raised

Question 10

What coagulation factor disorders are there?

Answer 10

• Von Willebrand disease
• Haemophilia A/B
• Coagulation factor inhibitors

Question 11

What is VWD?

Answer 11

• commonest inherited bleeding disorder
• AD
• mild bleeding disorder
• reduced levels of VWF
• Get mucocutaneous bleeding, bruising, post-op bleeding, menorrhagia and post-part I’m bleeding

Lab

• normal platelet count
• APTT can be normal or raised

Diagnosis
- FVIII, VWF Ag and function testing

Tx

• Desmopressin —> increase VWF release in endothelium
• Pooled plasma concentrates containing VWF

Question 12

What is haemophilia?

Answer 12

• Genetic variant in VIII or IX —> low plasma levels
• classified as severe, moderate or mild by plasma levels
• X-linked recessive, predominates in males
• therefore all the sons of affected males are normal, and all their daughters are carriers

Labs in A

• APTT increased
• Normal PT
• Decreased VIII

Tx

• prophylaxis with recombinant factor VIII/IX replacement in severe
• subcut emicuzimab