Bleeding + Platelet Disorders Flashcards
What are characteristics of bleeding due to platelet function defects?
Mainly in
- skin
- mucous membranes (e.g. petechiae, epistaxis, bleeding gums, menorragia)
- immediately after injury
What are characteristics of bleeding due to coagulation factors defects?
Bleeding into deep tissues incl.
- muscles
- joints
May be delayed
What is a usual clinical presenation of someone with Haemophilia A?
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.
What lab findings on clotting Studies would you expect in a patient with haemophilia A?
How would you confirm it?
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)
How if Haemophilia A treated?
- 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)
What is the epidemiology of Haemophilia A and B?
Haemophilia A: 1 in 5.000 males
Haemophilia B (1/4 of cases)
What investigations are done for diagnosis of Haemophilia B?
- Clotting assays: normal PT and TT, increased APTT
Confirmation: Factor IX assay
What is the most common inherited bleeding disorder?
What is it’s epidemiology?
Von-Willebrand disease (about 1% of population)
What is the aetiology of Von-Willebrand disease?
What is the most common sub-type?
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
How does a deficiency in vWF cause abnormal bleeding?
Decreased vWF function
1. Dysfunction platelet adhesion –> impaired primary haemostasis
2. Reduced binding of Factor VIII –> increased degradation –> decreased Factor VIII levels
How is von Willebrand disease diagnosed?
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
How can von Willebrand disease treated?
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
How would abnormal bleeding due to Warfrin overdose present on lab tests?
Interferes with intrinsic, extrinsic and common pathway
Abnormalities seen in
1. PT and APTT time prolonged (but PT time relatively more prolonged), normal TT
How does renal disease lead to coagulation disorders?
Renal failure can lead to inhibition of platelet function
What factors are replaced in cryoprecipitate?
REaplacement of Factor
VIII, XIII and fibrinogen
What is DIC?
Different aetiologies characterised by
1. increased, disseminated activation of coagulation with acute increased fibinolysis (–> increased clotting + bleeding)
Including end-organ disfunction
What lab-findings would suggest a diagnosis of DIC
- increased TT, PT and APTT (clotting factors are used up)
- Increased evidence of fibrine degradation (D-dimer)
- Fibrinogen assay (low - used up)
What are differnt aetiologies of thrombocytopenia?
- 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)
What is ITP?
What is its aetiology?
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,
What is the epidemiology of ITP?
How does the prognosis differ in children vs. adults?
2 peaks
- Children: peak incidence around 5, M=F, often triggered by infection and mild+ self-limiting within 12 months
- Adults young women (or old people), more likely to become chronic and treatment usually needed
What are the clinical features of ITP?
Usually bleeding from mucosal surfaces (e.g. gums, epistaxis) + petechiae, purpora, eccymoses and bruises
Potentially features of 2nd cause (e.g. SLE; RA)
What investigations should be done to diagnose ITP?
- 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)
How is ITP usually managed?
In children: usually no treatment required
In adults: only if life-threatening haemorrage
1. platelet transfution
Cortocosteroids
What are some causes of defects of platelet function?
- 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
What are some causes of Vit.K deficiency?
What coagulation abnormalities does it cause?
Anything that impaires fat absorbtion
1. e.g. pancreatic cancer, liver cirrhosis, etc.
Can present with increased bleeding + increase in PT and aPTT
What are the different aetiologies of DIC?
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
What coagulation factors are synthesised in the liver?
How does liver disease influence haemostasis?
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
