BLEEDING DISORDERS (PRIMARY HAEMOSTASIS) Flashcards
What are the causes of thrombocytopenia?
Idiopathic Immune Thrombocytopenic Purpura (Auto-ITP). These Ab do NOT activate the platelets. Instead they opsonize them for clearance
Thrombotic Thrombocytopenic Purpura/ Haemolytic Uremic Syndrome (TTP/HUS)
Disseminated Intravascular Coagulation (DIC) (both primary and secondary)
Heparin induced thrombocytopenia (HIT)
Thrombocytopenia in pregnancy
- Gestational Thrombocytopenia: physiologic adaptation of pregnancy, related to the increased plasma volume, pooling or consumption of platelets in the placenta, or other physiologic changes that occur in uncomplicated pregnancies
- HELLP / Pre-eclampsia, Eclampsia
Hypersplenism
Haematological malignancies (e.g. MDS, Myelofibrosis, leukaemia leading to bone marrow failure)
What are the causes of abnormal platelet function?
Inherited disorders (rare):
- Glanzmann’s thrombasthenia (2b-3a deficiency)
- Bernard-Soulier Syndrome (1b deficiency)
- Storage pool disease (deficiency in ADP in platelet granules)
Acquired disorders e.g. aspirin, renal failure
- Renal failure causes uraemia: abnormal platelet function
- Aspirin causes abnormal activation due to inhibition of TXA2 production
What are the causes of vessel wall disorders that lead to increased bleeding?
Hereditary vascular disorders
Acquired: Vit C deficiency (scurvy), high dose steroids, age
[IDIOPATHIC IMMUNE THROMBOCYTOPENIC PURPURA (AUTO-ITP)]
Acute ITP
- Peak age
- Female: Male
- Preceding infection
- Inset
- Platelet count
- Duration
- Spontaneous remission
- Peak age: children (2- 6 y/o)
- Female: Male –> 1:1
- Preceding infection : common
- onset: abrupt
- Platelet count: <20 000
- Duration: 2-6 weeks
- Spontaneous remission: common
[IDIOPATHIC IMMUNE THROMBOCYTOPENIC PURPURA (AUTO-ITP)]
Chronic ITP
- Peak age
- Female: Male
- Preceding infection
- Inset
- Platelet count
- Duration
- Spontaneous remission
- Peak age: Peak Age Children (2-6 y.o.) Adults (20-40 y.o.)
- Female: Male –>3:1
- Preceding infection : rare
- onset: abrupt- indolent
- Platelet count: <50 000
- Duration: Long-term
- Spontaneous remission: uncommon
[IDIOPATHIC IMMUNE THROMBOCYTOPENIC PURPURA (AUTO-ITP)]
What is the presentation of ITP?
- ITP patients usually will have severely low platelet count (<10)
- However, bleeding risk of ITP is surprisingly LOW for someone with such low plt count
- Suspect ITP in patient who has thrombocytopenia but otherwise asymptomatic
[IDIOPATHIC IMMUNE THROMBOCYTOPENIC PURPURA (AUTO-ITP)]
What is the management of ITP?
Platelet count >50,000: no symptoms, no treatment needed
Platelet count 20,000 – 50,000:
- If not bleeding, no treatment needed
- If bleeding, give steroids OR IVIG
Platelet count <20,000:
- If not bleeding, give steroids
- If bleeding, give steroids, IVIG AND hospitalize.
[THROMBOTIC THROMBOCYTOPENIC PURPURA]
What is the definition of TTP?
MAHA + low platelets and no identifiable cause
[THROMBOTIC THROMBOCYTOPENIC PURPURA]
What are the features of TTP (FATRN)?
- Fever
- Anaemia (MAHA)
- Thrombocytopenia
- Renal Failure (AKI) – not as common
- Neurological disturbances* – distinguishes TTP from HUS (TIA, Stroke, Altered mental status, Seizure etc)
[HUS] What are the features of HUS (RAT)?
- Renal Failure (AKI)* – distinguishes TTP from HUS
- Anaemia (MAHA)
- Thrombocytopenia
[HUS] How is HUS different from TTP?
- Renal failure is common (since this is the 1’ location of infection by E Coli / Shigella)
- Children more frequently affected (<5 YO)
- HUS is a/w E. coli 0517 phenotype (aka Enterohaemorrhagic E Coli - EHEC) or Shigella (releases shiga-toxins). No neurological disturbances
[TTP] What are the causes of TTP?
Pathophysiology of idiopathic/congenital TTP
- ADAMTS 13 protein absent (congenital) or autoantibodies against ADAMTS 13 (hence may require immunosuppression as part of treatment)
Causes of Secondary TTP: mechanism not so clear
- Drugs (eg: penicillin, clopidogrel)
- BM transplant
- SLE
- Malignancy
- Pregnancy
- Infection
[TTP/ HUS] What are the investigations for TTP/ HUS?
- FBC: Anaemia, thrombocytopenia
- Peripheral blood film: RBC fragments (schistocytes)
- Coagulation screen (PT/APTT), fibrinogen, D-dimer: normal in TTP (differentiate from DIC)
- Urine and Electrolytes: look for renal dysfunction (esp. in HUS)
- ADAMTS 13 level: turnover time takes too long. Hence as long as we suspect a TTP (aka MAHA, Low Plt, normal Coag Time) we will immediately plasmapheresis to give ADAMTS13!
Others: LFT, LDH, Direct Coombs Test, Urinalysis, ANA
[TTP] What is the management of TTP?
Daily plasma exchange (plasmapheresis)
- Mortality with management is 10-30% (rather than >90%)
- Exchange is better than plasma infusion (plasma contains healthy ADAMTS 13)
- Average number of exchanges for remission was 15.8 (range 3-36)
Normally we will NOT want to transfuse platelets during plasmapheresis due to risk of further MAHA (since plasmapheresis takes ~4hrs)
- EXCEPTION: if patient has active bleeding (eg: subdural haemorrhage)
[Heparin induced thrombocytopenia] What are the clinical features of HIT?
Fall in platelets by more than 50%
Within 5-10 days after commencing heparin
Associated with high risk of thrombosis (both venous and arterial)
- leading to amputation
- Thrombotic Sequalae (especially if arterial): skin necrosis, limb gangrene, organ infarction
Bleeding is rare because the platelet count nadir typically does not drop below 20,000/microL. However, bleeding has been reported
