Bleeding + Platelet Disorders

Question 1

What are characteristics of bleeding due to platelet function defects?

Answer 1

Mainly in
- skin
- mucous membranes (e.g. petechiae, epistaxis, bleeding gums, menorragia)
- immediately after injury

Question 2

What are characteristics of bleeding due to coagulation factors defects?

Answer 2

Bleeding into deep tissues incl.

1. muscles
2. joints

May be delayed

Question 3

What is a usual clinical presenation of someone with Haemophilia A?

Answer 3

Haemophilia A: X-linked recessive (usually, can be spontaneous and very rarely auto-immune) deficiency of Factor VIII

Bleeding into joints+muscles
Disporportinoate bleeding after minor trauma
GI haemorrhage etc.

Question 4

What lab findings on clotting Studies would you expect in a patient with haemophilia A?

How would you confirm it?

Answer 4

PT and TT normal

APTT prolonged –> (Intrinsic pathways prolonged as Factor VIII missing + factor VIII important co-factor for Factor IX)

**Confirmation: Assay of factor VIII **(as Von Willebrand disease might present with similar findings)

Question 5

How if Haemophilia A treated?

Answer 5

1. Avoid NSAIDs and IM drugs

Best treatment for severe cases:
Prophylactic treatment with recombinant human factor VIII (half-life 12h, injection ever 2nd day)

Others
- in mild cases: desmoporession (increased release of VWF VIII from endothelial cells)

Question 6

What is the epidemiology of Haemophilia A and B?

Answer 6

Haemophilia A: 1 in 5.000 males
Haemophilia B (1/4 of cases)

Question 7

What investigations are done for diagnosis of Haemophilia B?

Answer 7

1. Clotting assays: normal PT and TT, increased APTT

Confirmation: Factor IX assay

Question 8

What is the most common inherited bleeding disorder?

What is it’s epidemiology?

Answer 8

Von-Willebrand disease (about 1% of population)

Question 9

What is the aetiology of Von-Willebrand disease?

What is the most common sub-type?

Answer 9

Inherited (caused by mutation in the von Willebrand gene):
* Type 1 and 2: autosomal dominant inheritance
* Type 1: mild to moderate deficiency of vWF and Factor VIII **(most cases) **
* Type 2 dysfunctional vWF
* Type 3: autosomal recessive disorder –> complete absence of vWF and Factor VIII

Acquired
* E.g. due to lymphoproliferative disorders, autoimmune disorders( SLE), Cardiovascular (e.g. Aortic stenosis, ventricular septal defect), drugs (e.g. valproic acid)

vWF deficiency leads to VIII deficiency as VWF transports and stabilises factor VIII

Question 10

How does a deficiency in vWF cause abnormal bleeding?

Answer 10

Decreased vWF function
1. Dysfunction platelet adhesion –> impaired primary haemostasis
2. Reduced binding of Factor VIII –> increased degradation –> decreased Factor VIII levels

Question 11

How is von Willebrand disease diagnosed?

Answer 11

Often coagulation screen is normal, might have increased APTT if Factor VIII is low

Now: Ristocetin cofactor assay: failure of platelet aggregation or a ristocetin cofactor level < 30 IU/dL

Question 12

How can von Willebrand disease treated?

Answer 12

Often no treatment necessary as sub-clinical in many cases

Mild cases
- tranexamic acid or desmopressin(release VWF from endothelial cells)

Moderate-severe cases
Intermediate purity factor VIII concentrate (contains VWF and factor VIII) + other formulations with VWF replacmenets

Question 13

How would abnormal bleeding due to Warfrin overdose present on lab tests?

Answer 13

Interferes with intrinsic, extrinsic and common pathway

Abnormalities seen in
1. PT and APTT time prolonged (but PT time relatively more prolonged), normal TT

Question 14

How does renal disease lead to coagulation disorders?

Answer 14

Renal failure can lead to inhibition of platelet function

Question 15

What factors are replaced in cryoprecipitate?

Answer 15

REaplacement of Factor
VIII, XIII and fibrinogen

Question 16

What is DIC?

Answer 16

Different aetiologies characterised by
1. increased, disseminated activation of coagulation with acute increased fibinolysis (–> increased clotting + bleeding)

Including end-organ disfunction

Question 17

What lab-findings would suggest a diagnosis of DIC

Answer 17

1. increased TT, PT and APTT (clotting factors are used up)
2. Increased evidence of fibrine degradation (D-dimer)
3. Fibrinogen assay (low - used up)

Question 18

What are differnt aetiologies of thrombocytopenia?

Answer 18

1. Inherited (rare) vs aquired (more common)

Out of the aquired ones
1. Decreased Production(e.g. Acute leukaemias, aplastic anaemias, cytotoxic chemotherapy)

2. Increased consumption (DIC, haemorrhage, TTP)

3. Increased destruction (ATP, alloimmune thrombocytopenia, drug-induced (e.g. heparin), post-infection

4. Pooling in Spleen (Hypersplenism)

Question 19

What is ITP?

What is its aetiology?

Answer 19

Idiopathic (formerly autoimmune) thrombocytopenia purpura

Autoimmune antibody production against platelts –> usually IgG against platelet receptors

Can be idiopathic or because of other underlying diseases (e.g. CLL/lymphomas, other auto-immune diseases,

Question 20

What is the epidemiology of ITP?

How does the prognosis differ in children vs. adults?

Answer 20

2 peaks

1. Children: peak incidence around 5, M=F, often triggered by infection and mild+ self-limiting within 12 months
2. Adults young women (or old people), more likely to become chronic and treatment usually needed

Question 21

What are the clinical features of ITP?

Answer 21

Usually bleeding from mucosal surfaces (e.g. gums, epistaxis) + petechiae, purpora, eccymoses and bruises

Potentially features of 2nd cause (e.g. SLE; RA)

Question 22

What investigations should be done to diagnose ITP?

Answer 22

1. Blood count + film: thrombocytopenia (normal size if acute, large platelets if chronic)

potentially testing for 2nd causes
1. auto-antibodies (incl. ANA; anti-DNA, anticardiolipin

To exclude other differentials
1. Blood count + film for TTP + leukaemia
2. Coagulation screen for DIC
3. ? BM aspirate to exclude leukaemia (in ITP: normal megakariocyte number+ size)

Question 23

How is ITP usually managed?

Answer 23

In children: usually no treatment required

In adults: only if life-threatening haemorrage
1. platelet transfution

Cortocosteroids

Question 24

What are some causes of defects of platelet function?

Answer 24

1. Usually drugs, incl. aspirin, clopidogrel, NSAIDs)

Other conditions
1. myelodysplastic syndrome/ AML (pt intrinsically abnormal)
2. renal failure (accumulation of wast produt inactivates pt)
3. DIC

Question 25

What are some causes of Vit.K deficiency?
What coagulation abnormalities does it cause?

Answer 25

Anything that impaires fat absorbtion
1. e.g. pancreatic cancer, liver cirrhosis, etc.

Can present with increased bleeding + increase in PT and aPTT

Question 26

What are the different aetiologies of DIC?

Answer 26

Many different causes can cause it

Most common ones include
1. Sepsis + infections
2. Different trauma
3. Obstetric complications
4. Malignancies
5. But many others aswell

Question 27

What coagulation factors are synthesised in the liver?

How does liver disease influence haemostasis?

Answer 27

Almost all excluding TF (III) , most importantly II, VII, IX, X, XI, and fibrinogen

+ can cause VIT K deficiency

Leading to increased PT and APTT BUT chronic liver diase is often a prothrombic state