Acquired bleeding disorders

Question 1

What are the causes of acquired bleeding disorders?

Answer 1

• Vit K deficiency
• Liver disease
• Massive transfusion syndrome
• Disseminated intravascular coagulation
• Iatrogenic
• Acquired inhibitors

Question 2

How can you tell if the bleeding disorder is due to a deficiency or the presence of an inhibitor?

Answer 2

• If activated partial thromboplastin time is prolonged repeat with 50:50 mix patient:normal plasma.
• Significant correction = deficiency
• No correction = inhibitor

Question 3

Which coagulation factors will be affected by a vit K deficiency?

Answer 3

(2)II, (7)VII, (9)IX & (10)X

Question 4

What are the possible causes of a vit K deficiency?

Answer 4

• Obstructive jaundice
• Prolonged nutritional deficiency
• Broad spectrum antibiotics
• Neonates (classical 1-7 days)

Question 5

Why do patients with liver disease develop coagulopathies?

Answer 5

The liver is essential for the maintenance of normal level of coagulation factors.

Question 6

What are patients with cirrhotic coagulopathy at risk of?

Answer 6

Severe bleeding from routine, invasive procedures (e.g. liver biopsies, dental extractions). Major source of morbidity and mortality in patients with liver disease.

Question 7

What are the pathological features of impaired haemostasis in liver disease?

Answer 7

• Thrombocytopenia
• Platelet dysfunction (plasmin induced cleavage of surface glycoproteins
• Reduced plasma concentration of all coagulation factors (reduced synthesis) except F(8)VIII
• Delayed fibrin monomer polymerisation due to altered fibrinogen glycosylation (xs sialic acid)
• Excessive plasmin activity

Question 8

What is a ‘massive transfusion’?

Answer 8

• Transfusion of a volume equal to the patient’s total blood volume in less than 24 hours

OR

• 50% blood volume loss within 3 hours

Question 9

What haemostatic abnormalities are possible in the case of a massive transfusion?

Answer 9

• Due to dilutional depletion of platelets and coagulation factors
• Due to DIC - risk factors are extensive trauma, head injury, prolonged hypotension
• Due to underlying disease, eg liver or renal drug treatment or surgery

Question 10

What are the dilutional effects on haemostasis?

Answer 10

• Thrombocytopenia - at least 7-8 litres in adults usually transfused before problems are likely
• Coagulation factor depletion - mainly factors (5)V & (8)VIII and fibrinogen
• DIC common
• Citrate toxicity: uncommon - hypothermia and neonates - increased susceptibility
• Hypocalcaemia - no clinically significant effect on coagulation

Question 11

What is the pathophysiology of DIC?

Answer 11

1. ‘Trigger’
2. Local activation of coagulation
3. Intravascular coagulation
4. Consumption of clotting factors & platelets and fibrin deposition
5. Microvascular thrombosis: due to above leading to tissue ischaemia and organ dysfunction
6. Activation of fibrinolysis
7. Widespread bleeding elsewhere due to the consumption of clotting factors, activation of fibrinolysis etc
8. Microangiopathic haemolysis

Question 12

What are the possible causes of acute DIC?

Answer 12

• Sepsis
• Obstetric complications
• Trauma/Tissue necrosis
• Acute intravascular haemolysis eg ABO incompatible blood transfusion
• Fulminant liver disease

Question 13

What are the possible causes of chronic DIC?

Answer 13

• Malignancy
• End stage liver Disease
• Severe localised intravascular coagulation
• Obstetric : retained dead foetus

Question 14

What laboratory tests are required in DIC?

Answer 14

• FBC and Blood film
• Coagulation screen: PT (70% prolonged), APTT (50% prolonged), TCT (usually prolonged)
• Fibrinogen Concentration
• FDP or D-Dimer (elevated in 85%)
• There is not one single diagnostic test: scoring systems are sometimes used.

Question 15

How should DIC be managed?

Answer 15

Treat underlying cause:

• Antibiotics
• Obstetric intervention
• Chemotherapy/ATRA/tumour resection

Supportive Treatment:

• maintain tissue perfusion
• Co-ordinate invasive procedures
• (Folic acid and Vitamin K to support recovery period especially if illness prolonged)
• Platelet Transfusion if platelets 1.5: FFP 15ml/kg
• Fibrinogen

Question 16

Which drugs potentiate the Warfarin effect?

Answer 16

• Cimetidine
• Ampicillin (oral)
• Amiodarone
• NSAID’s
• Sulphinpyrazone
• Chlorpromazine
• Cotrimoxazole
• Sulphonylureas
• Erythromycin
• Corticosteroids
• Cephlosporins

Question 17

Which drugs anatgonise the Warfarin effect?

Answer 17

• Cholestyramine
• Spironolactone
• Rifampicin
• Carbamazepine
• Vitamin K

Question 18

How should heparin be monitored?

Answer 18

• Anticoagulant effects of UFH can be monitored by tests sensitive to the anti-thrombin and/or anti-(10)Xa effects of heparin.
• For purposes of full anticoagulation with UFH, the APTT is most commonly used assay.
• Alternatives are: heparin level by protamine titration, heparin level by anti-(10)Xa assay, calcium thrombin time.
• In situations where it is desirable to monitor the effect of LMWH, anti-(10)Xa assays are used.
• The APTT is not sensitive to LMWH

Question 19

Describe the management of bleeding due to overanticoagulation with heparin.

Answer 19

(1) Stop infusion
(2) Consider protamine administration 1mg neutralises 100IU of heparin Maximum 40mg.
(3) Effects of protamine on LMWH are less predictable and are complex

Question 20

What is the difference between low molecular weight heparin vs unfractionated heparin?

Answer 20

• LMWH: Higher ratio of anti-(10)Xa to anti-(2)IIa activity.
• Improved bioavailability.
• Longer half life allowing once daily administration.
• More predictable anticoagulant response: monitoring is not routinely required.