Table 3.

Main features of inherited thrombocytopenias.

Form	Disease	Inheritance	Degree of Thrombocytopenia	Key Laboratory Features	References
Syndromic	Amegakaryocytic thrombocytopenia with radio-ulnar synostosis (ATRUS)	AD	severe	Normal platelet size and morphology	[19,20]
	Baraitser–Winter syndrome 1 with macrothrombocytopenia	AD	absent	Macrothrombocytopenia; leukocytosis with eosinophilia, leukopenia	[27]
	FLNA-related thrombocytopenia	XL	moderate	Macrothrombocytopenia; impaired platelet aggregation GPVI-triggered; heterogeneous α-granules, occasionally giant; abnormal distribution of FLNa	[32]
	GATA-1-related disease	XL	severe	Macrothrombocytopenia; reduced platelet aggregation by collagen and ristocetin; reduced α-granule content and release	[17]
	GNE-related thrombocytopenia	AR	from mild to severe	Macrothrombocytopenia	[48]
	Gray platelet syndrome	AR	moderate/severe	Macrothrombocytopenia; grey or pale platelets; dyserytropoiesis; absence of α-granules; defective TRAP-induced platelet aggregation	[23]
	Paris-Trousseau thrombocytopenia, Jacobsen syndrome	AD	severe	Macrothrombocytopenia; defective platelet aggregation by thrombin; giant α-granules	[15]
	Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease	AR	moderate	Small platelets; eosinophilia; reduced platelet spreading; decreased platelet dense granules	[29]
	PTPRJ-related thrombocytopenia	AR	moderate/severe	Microthrombocytopenia; impaired activation by the GPVI-specific agonist convulxin and the thrombin receptor-activating peptide but normal response to ADP	[51]
	SRC-related thrombocytopenia	AD	moderate/severe	Platelets deficient in granules and rich in vacuoles	[50]
	Stormorken syndrome	AD	moderate/severe	Howell-Jolly bodies in red blood cells; enhanced annexin V binding, defective GPIIb/IIIa activation (PAC-1)	[41]
	Takenouchi-Kosaki syndrome with macrothrombocytopenia	AD	absent	Macrothrombocytopenia, abnormal platelet spreading and filopodia formation	[47]
	Thrombocytopenia-absent radius syndrome (TAR)	AR	severe	Normal platelet size and morphology, thrombocytopenia	[24]
	Thrombocytopenia and erythrokeraderma	AR	moderate	Thrombocytopenia and presence of 3-keto-dihydrosphingosine in plasma	[37]
	Thrombocytopenia, anemia and myelofibrosis	AR	mild/moderate	Macrothrombocytopenia, anemia	[39]
	Wiskott–Aldrich syndrome	XL	severe	Microthrombocytopenia; Reduced α/δ granules release	[45]
	X-linked thrombocytopenia	XL	mild/moderate	Microthrombocytopenia; Reduced α/δ granules release	[45]
Non-syndromic	ACTN1-related thrombocytopenia	AD	mild	Macrothrombocytopenia	[28]
	Bernard Soulier syndrome monoallelic biallelic	AD AR	mild moderate/severe	Macrothrombocytopenia; lack of platelet agglutination to ristocetin with normal aggregation to other agonists; severe reduction or complete lack of GPIb/IX/V	[33]
	CYCS-related thrombocytopenia	AD	mild	Normal platelet size and morphology	[30]
	FLI1-related thrombocytopenia	AD/AR	moderate	Reduced platelet aggregation in response to collagen and PAR-1 agonists; δ-granule deficiency	[15]
	FYB-related thrombocytopenia	AR	moderate/severe	Microthrombocytopenia; increased expression of P-selectin and PAC-1 by resting platelets but impaired upon stimulation with ADP	[16]
	GFI1b-related thrombocytopenia	AD/AR	mild/moderate	Macrothrombocytopenia; dyserytropoiesis; reduced α-granule content and release; diminished expression of GPIbα, red cell anisocytosis	[18]
	IKZF5-related thrombocytopenia	AD	absent	Thrombocytopenia; deficiency of platelet alpha granules.	[21]
	ITGA2B/ITGB3-related thrombocytopenia	AD	mild/moderate	Macrothrombocytopenia; reduced GPIIb/IIIa; defective GPIIb/IIIa activation (PAC-1)	[35,36,54]
	PT-VWD	AD	mild/moderate	Macrothrombocytopenia; increased response to ristocetin and decreased VWF-ristocetin cofactor activity (VWF:RCo) Mixing tests discriminate the plasmatic (VWD type2B) from platelet (PT-VWD) origin of hyperreactivity to ristocetin	[36,76,77]
	PRKACG-related thrombocytopenia	AR	severe	Macrothrombocytopenia; defective platelet αIIbβ3 activation and P-selectin exposure in response to TRAP6; defective Ca2+ mobilization in response to thrombin	[40]
	THPO-related thrombocytopenia	AD	mild	Normal or slightly increased platelet size	[26]
	TRPM7-related thrombocytopenia	AD	mild/moderate	Macrothrombocytopenia; aberrant distribution of granules	[42]
	Tropomyosin 4 (TPM)-related thrombocytopenia	AD	mild	Macrothrombocytopenia	[43]
	TUBB-1-related thrombocytopenia	AD	mild	Macrothrombocytopenia; platelet anisocytosis	[44]
	SLFN14-related thrombocytopenia	AD	mild/moderate	Macrothrombocytopenia; δ-granule deficiency with decreased ATP secretion in response to ADP, collagen and TRAP-6	[49]
Forms predisposing to additional diseases	ANKRD26-related thrombocytopenia	AD	mild/moderate	Reduced α-granules in some patients	[13]
	Congenital amegakaryocytic thrombocytopenia (CAMT)	AR	severe	Elevated serum levels of TPO	[22]
	DIAPH1-related thrombocytopenia	AD	mild/severe	Macrothrombocytopenia	[31]
	ETV6-related thrombocytopenia	AD	mild/moderate	Decreased ability of platelets to spread on fibrinogen covered surfaces; abnormal clot retraction	[14]
	Familial platelet disorder with predisposition to hematological malignancies (FPD/AML)	AD	moderate	Abnormal aggregation in response to multiple agonists; δ (occasionally α)-granule deficiency	[25]
	MYH9-related disease	AD	mild/severe	Macrothrombocytopenia; Döhl-like body cytoplasmic leukocyte inclusions	[38]
	Thrombocytopenia associated with sitosterolemia		moderate/severe	Macrothrombocytopenia; hyperactivatable platelets with constitutive binding of fibrinogen to αIIbβ3 integrin; shedding of GPIbα; impaired platelet adhesion to von Willebrand factor	[46]