Platelet disorders Flashcards
Potential mechanisms of ITP
- Dysregulation of T-cells that has direct cytotoxic effect of plt and megakaryocytes
- Autoantibodies against glycoproteins on megakaryocytes impairing megakaryocyte proliferation and platelet production
- Autoantibodies against glycoproteins on platelets (GPIIb-IIIa, GPIb-IX) resulting in increased clearance by R.E.S.
- Platelet opsonization
- Decreased levels of regulatory T cells activity
Explain FNAIT. What is the most common antigen target on platelets. One feature that distinguishes from HDFN.
FNAIT= Maternal IgG antibody against paternal antigen on fetal platelets. Antibody crosses placenta leading to opsonization and destruction of fetal platelets
Most common: mom HPA 1b/1b (2% of population)
dad HPA 1a/1a
baby has HPA 1a on its platelets
Less common: HPA 5b (whites), HPA-4b (asians), HPA-3b
*NAIT can occur with the first pregnancy, HDN only occurs in the subsequent pregnancy.
MOA of the following anti-platelets:
ASA, Abciximab, Prasugrel, Ticagrelor.
a. Ticagrelor: Reversibly inhibits ADP P2Y12 receptor for ADP → inhibits ADP-dependent and TXA2 platelet aggregation
b. Prasugrel, plavix: Same as above but irreversible
c. Abciximab: Inhibits GPIIbIIIa → fibrinogen can’t bind → inhibits platelet aggregation
d. ASA: COX 1 inhibitor–>blocks TxA2–>less aggregation
What’s the evidence for EC-ASA in secondary prevention of VTE?
WARFASA
ASA 100mg OD vs placebo for patients who completed 6-18mo of OAC for VTE
Primary outcome: recurrent VTE
Outcome: 6.6% vs 11.2%
ASPIRE
ASA 100mg OD vs placebo for patients who completed 1.5-24mo of OAC
Primary outcome: recurrent VTE
Outcome: 14% vs 18%
Pooled analysis of the two trials showed a 32% reduction in VTE recurrence (HR 0.68; P=0.007)
Name 4 MYH9 disorders
May-Hegglin- Just heme features
Epstein Syndrome- No dohle-body inclusions
Fetchner syndrome=fucked, all features.
Sebastian’s Syndrome
- MYH9 encodes non-muscle myosin Ia heavy chain
- Morph- Dohle-like WBC inclusions, giant platelets, thrombocytopenia.
- Non-heme features: nephritis, deafness, cataracts
Causes of pseudothrombocytopenia
EDTA effect (plt clumping) Megathrombocytes Clotted sample Abciximab-induced high protein states ?multiple myeloma elevated lipids
L: EDTA, platelet satellism, giant platelets
Bernard Soulier
Plt size, Plt number, Plt aggregation, Flow cytometry
Bernard Soulier: Deficiency in GP Ib/IX Plt Size: Large Plt Number: Low Platelet aggregation: Absent ristocetin response but normal to every other agonist (GP1b/IX) Receptor lost: vWF Flow cytometry: CD42b (expression)
Glanzmann Thrombothesenia
Plt size, Plt number, Plt aggregation, Flow cytometry.
Plt Size: normal Plt Number normal Platelet aggregation: abnormal to everything except ristocetin (GP2b/3a) Receptor lost: Fibrinogen Flow cytometry: CD41/CD61
Name 3 infections associated with ITP
H. Pylori HIV Hepatitis C EBV Intracellular Parasites (malaria, babesia)
Glanzmann thrombasthenia, what 2 vaccinations do you need to give
- Prevnar
- Pneumococcal
(can be associated with leucocyte adhesion disease)
Do not give live vaccines!
What is the mechanism of EDTA induced thrombocytopenia?
Results from a “naturally occurring” platelet autoantibody (IgM) directed against a concealed epitope on platelet membrane glycoprotein (GP) IIb/IIIa that becomes exposed by EDTA-induced dissociation of GPIIb/IIIa.
What class of proteins is implicated in platelet refractoriness?
Class I HLA (HLA-A and HLA-B are the only clinically significant and typically the only ones tested).
HPA very rare.
Causes of macrothrombocytopenia
- MYH9 disorders
- ITP
- BSS
- Grey Platelet syndrome
- Montreal plt syndrome
- X-linked dyserythropoietisis
- Autosominal dominant thrombocytopenia
Treatment of FNAIT
Transfusion of HPA-compatible platelets, which can be collected and washed from the mother or from an antigen-negative donor.
IVIG (1.0 g/kg/d for 1 to 3 days depending on response) and methylprednisolone also may decrease the rate of platelet destruction and can be used as adjunctive therapy.
usually resolves within 2 to 4 weeks spontaneously
What percentage of children will experience spontaneous recovery of ITP?
75% of patients achieving a complete remission by 6 months from presentation.
Which of the inherited thrombocytopenias can display spontaneous resolution in childhood?
Thrombocytopenia-absent radius syndrome