Disorder Defect Platelet count Blood Film ADP
[2μM] 		ADP
[5-10 μM] 		Collagen
[1 μg/mL] 		AA
[100 μM ]		 Adrenaline [10 μM ] Ristocetin [1.2 mg/mL] Ristocetin [0.5 mg/mL Thrombin
[0.2 U/mL]		 Platelet Nucleotides Platelet Procoagulant Activity Comments
Normal None Normal
[150-400 x 109/L		 No abnormality Primary and secondary wave aggregation seen Secondary wave aggregation only Normal Normal Normal Normal Absent   Normal ATP:ADP ratio >2.0 but this can vary from lab to lab Normal None!
Glanzmann's Thrombasthenia
[see comments]		 Defect in GpIIb/IIIa receptor Normal
No abnormality Absent Absent Absent Absent Absent Normal
[although maximal light transmission is decreased]		 Absent Absent Normal May be reduced Flow cytometry shows decreased expression of the Gp IIb/IIIa receptor
A similar picture will be seen in afibrinogenaemia as fibrinogen is essential for normal platelet aggregation via the GpIIb/IIIa receptor
Bernard Soulier Syndrome
[see comments]		 Defect in GpIb-V-IX receptor Reduced MPV ↑
Giant platelets Thrombocytopaenia		 Normal Normal Normal Normal Normal Absent Absent Normal Normal May be reduced Important to check that VWF levels are normal.
Flow cytometry shows decreased expression of the Gp Ib receptor and may show increased expression of the Gp IIb/IIIa receptor due to the presence of large platelets.
Velocardiofacial Syndrome Chromosomal deletion of 22q11.2 including the GpIb beta gene May be reduced
MPV ↑
Giant platelets Thrombocytopaenia		 Normal Normal Normal Normal Normal Absent Absent Normal Normal May be reduced The deleted chromosomal region in >90% of VCFS patients includes the GpIb beta gene, encoding for one subunit of the platelet GpIb-V-IX receptor.
Aspirin &
NSAIDs		 Inhibit Cyclooxygenase [COX-1] either irreversibly - Aspirin or reversibly - NSAIDs Normal
No abnormality Primary wave only
[Absent second wave]		 Primary wave only
[Absent second wave]		 Decreased or absent Absent Decreased Normal Absent        
Cyclooxygenase Deficiency [COX-1] & defects in Thromboxane synthesis
[Similar to Aspirin]		 COX-1 deficiency due either to a complete absence of the enzyme or a functional abnormality. Leads to defective TxA2 generation Normal No abnormality Primary wave only
[Absent second wave]		 Primary wave only
[Absent second wave]		 Decreased or absent Absent Decreased Normal Absent        
Gp1a/IIa & GpVI deficiency
[Collagen receptor deficiency]		 Defect in the platelet collagen receptor Normal Normal Normal Normal Absent Normal Normal Normal Absent Normal Normal Normal GpIa and GpVI are the major collagen receptors on platelets.
Gray Platelet Syndrome
[a-granule deficiency]		 Deficiency of α-granules Often decreased Platelets appear gray in colour - sometimes referred to as platelet 'ghosts'
Large platelets		 Normal or decreased Normal or decreased Variable but usually decreased Normal Normal Normal Absent Decreased/Absent     Decreased α-granules on EM
Association with myelofibrosis
2B VWD Dysfunctional VWF protein Decreased Thrombocytopaenia Normal Normal Normal Normal Normal Normal Increased Normal Normal Normal Type 2B VWD and Platelet-Type VWD can be distinguished from each other by:
- Mixing studies
- Genetic Tests
- A rapid method for distinguishing the two is to add cryoprecipitate to PRP. In Platelet-Type VWD this causes platelet aggregation but does not in Type 2B VWD
Platelet-type VWD Mutation in the GpIb receptor - usually within the hinge region of the protein Decreased Thrombocytopaenia Normal Normal Normal Normal Normal Normal Increased Normal    
Dense Granule Deficiency
Defect in dense granules Normal Usually normal Normal Absent Decreased Normal Absent secondary wave Primary Wave Only Absent Normal or decreased Increased ATP:ADP ratio Decreased or normal Decreased dense granules on EM
Decreased ATP release by lumiaggregometry
Albinism in patients with Hermansky Pudlak disorder or Chediak Higashi syndrome
Secretion Defect Dense granules are present but not released Normal Usually normal Normal Absent Decreased Normal Absent secondary wave ?? Primary Wave Only Absent Normal or decreased Normal Normal  
Montreal Platelet Syndrome   Recent Data has highlighted that may be due to Type 2B VWD.  Jackson et al Blood 2009;113:3348-3351.
Scott Syndrome Defect in platelet procoagulant activity characterised by impaired transmembrane migration of procoagulant phosphatidylserine
Other disorders can also be associated with defective PCA		 Normal Normal Normal Normal Normal Normal Normal Normal Absent Normal Normal Decreased In some cases appears due to a mutation within the ABCtransporter A1 [ABCA1] gene or to a trans-acting regulatory gene sequence that controls its expression
Decreased PF3a
ADP antagonists e.g. Clopidogrel
ADP receptor [P2Y12] abnormality
 Inhibition of the ADP receptor Normal Normal Absent Absent Normal Normal Normal Normal Absent Normal Normal   Important to check that VWF levels are normal.
Flow cytometry shows decreased expression of the Gp Ib receptor and may show increased expression of the Gp IIb/IIIa receptor due to the presence of large platelets.
Signal Transduction Disorders Multiple - poorly defined Normal Normal Primary wave only
[Absent second wave]		 Primary wave only
[Absent second wave]		 Decreased ??? ??? Normal Absent   May be reduced ? Normal Granule contents but there may be a defect in ADP release
Myeloproliferative Disorders   Decreased or increased   Inconsistent findings Inconsistent findings Inconsistent findings Inconsistent findings Inconsistent findings Inconsistent findings Absent Inconsistent findings May have an acquired SPD   Membrane GpIIb/IIIa expression may be reduced
Uraemia Acquired SPD May be decreased   Normal Decreased Normal or decreased Normal or decreased Decreased Normal or decreased Absent Normal or decreased Normal or decreased Decreased GPIb and IIb/IIIa expression may be reduced
Liver Disease Multiple May be decreased May show Thrombocytopaenia Primary wave only
[Absent second wave]		 Primary wave only
[Absent second wave]		 Decreased   Primary wave only
[Absent second wave]		 Normal or decreased Absent Decreased      
DIC Multiple May be decreased May show Thrombocytopaenia Decreased Decreased Decreased Decreased Decreased Decreased Absent Decreased   Acquired SPD  
Cardio-Pulmonary Bypass Acquired SPD May be decreased May show Thrombocytopaenia May be decreased May be decrease May be decreased May be decreased May be decreased Decreased Absent May be decreased Deficiency of α and dense granules