Acquired defects of haemastasis

Question 1

Why is there a risk of increased bleeding in CPB?

Answer 1

• administration of preoperative aspirin
But mostly due to a DEFECT IN PLATELETS.
• turbulence/stress in the machine = MAHA & similar damaging affect on platelets [drop in platelet count by up to 60%]
• contact with ‘alien’ surface = activation of fibrinolysis, inflammatory mediators, complement
• hypothermia may be experienced in surgery – this is associated with defective thromboxane A2 synthesis by platelets = impaired aggregation

Question 2

How do we manage the increased risk of bleeding in CPB?

Answer 2

Previously we gave aprotinin and transfusions.

Now, if bleeding we give platelets.

Question 3

What is aprotinin? Why do we avoid it? Why do we avoid giving transfusions in CPB pnts?

Answer 3

• APROTININ is an inhibitor of plasmin and kallikrein. it used to be used to decrease bleeding risk but was associated with increased risk of MI, renal failure and stroke. [These risks are not seen with other antifibrinolytics eg tranexamic acid]
• if patients bleed in CPB– avoid transfusion (associated with renal failure, infection) and give platelets

Question 4

What bleeding symptoms are associated with uraemia?

Answer 4

• The clinical picture including bruising, epistaxis, Gi bleeding and intracranial haemorrhage
- uraemic haemorrhage can be fatal

Question 5

Why is there a bleeding tendency with uraemia patients?

Answer 5

A. Uraemia associated
- Platelet dysfunction (due to storage pool defects, decreased TXA2 production & increased plt Ca)
- Defective interaction between platelet and vessel wall
- Low haematocrit (i.e. anemia)
- Nitric oxide production
B. Dialysis associated – activation of coagulation because of contact between dialysis membrane and the blood; anticoagulants used in dialysis
C. Medication associated – antiplatelet agents, anti-inflammatory drugs, antibiotics

Question 6

Why is there platelet dysfunction?

Answer 6

•platelet dysfunction is caused by guanidosuccinic acid – which is produced by an abnormal ammonia detoxification pathway that occurs in uraemia

Question 7

Management of uraemic haemorrhage

Answer 7

o correct anaemia (transfusion)
o DDAVP
o Cryoprecipitate
o Conjugated oestrogens (5 days of IV 0.6mg/kg.
Transdermal HRT patches one patch twice a week)

Question 8

Pathogenesis of DIC

Answer 8

1. TF/ other procoagulant material is directly released into circulation (this can be secondary to trauma/malignancy)
2. TF expression can be increased (Either due to endothelial damage (sepsis, burns) or provoked by bacterial toxins/other cytokines (TNFalpha, IL1,6,10))
3. Decreased expression of thrombomodulin (secondary to endothelial damage)
4. Increased degradation (by neutrophils) of antithrombin +/ impaired synthesis of antithrombin
5. high levels of PAI-1 which depresses fibrinolysis

Question 9

4 main causes of DIC

Answer 9

1. Infections (g-ve sepsis, malaria)
2. Cancer (acute leukaemia)
3. obstetric (septic abortion, placental abruption, eclampsia)
4. tissue necrosis (burns, trauma, liver disease)

Question 10

How do you get organ failure in DIC?

Answer 10

• Widespread fibrin deposition within circulation =
o MAHA (shistocytes on blood film)
o Compromised blood supply to organs → multiple organ failure
• particularly wary of kidney, brain, heart, liver, lung damage

Question 11

Mx of DIC

Answer 11

you must treat the cause
•supportive measures can be given in the mean time
o blood transfusion if blood loss/anaemia is severe
o replacement coagulation factors (FFP/PCC)
o platelet transfusions 1unit/10kg body weight when it drops below 50
o cryoprecipitate when fibrinogen <0.8g/l
o Protein C/ TFPI have some use in sepsis induced DIC [PC causes haemorrhage]

Question 12

Ix of DIC

Answer 12

• Prolonged PT,APTT, TT with Increased FDP and D-dimer
• low fibrinogen, protein C, antithrombin, platelet
• A diagnosis of DIC is difficult but an ISTH score >=5 can be suggestive