Table 1.

Genetic impact, definition and coagulation testing of inherited bleeding disorders

Disorder	Genetic impact	Definition	Coagulation testing
von Willebrand disease2,19,20	vWF gene / 12p (13.31) Autosomal dominant: types 1, 2A, 2B, 2M Autosomal recessive: types 2N, 3 In pregnancy: ♦ Type 1: vWF/factor VIII level normal ♦ Type 2: vWF/factor VIII level increased	Prevalence 1300/100 000 Mucocutaneous bleeding Family history vWF deficiency	Low vWF antigen level and functional assay result Prolonged aPTT Prolonged bleeding time or closure time Low factor VIII level Quantitative deficiency: types 1 and 3 Qualitative deficiency: types 2, 2A, 2B, 2M, 2N
Hemophilia A21–23	X-linked recessive (male) factor VIII F8; Xq28 Severe–moderate in 70% of cases Mild in 30% of cases Female carrier is heterozygote	Prevalence in males 17/100 000 (1/5000) Factor VIII level < 2% of normal Factor VII level 2%–25% of normal In about 50% of cases	Prolonged aPTT Low factor VIII level aPTT usually low normal
Hemophilia B24–26	X-linked recessive (male) factor IX F9; Xq27 Severe–moderate in 70% of cases Mild in 30% of cases Female carrier is heterozygote	Prevalence in males 4/100 000 (1/30 000) Factor IX level < 2% of normal Factor IX level 2%–25% of normal In about 50% of cases	Low factor IX level Prolonged aPTT aPTT usually normal, low factor IX level
Factor XII deficiency27	—	—	Low factor XII level Prolonged aPTT
Factor XIII deficiency28	Autosomal recessive	Prevalence 1/2 000 000–1/5 000 000 Hemorrhagic diathesis Habitual abortion Defective wound healing	Low factor XIII level aPTT and INR normal
Inherited platelet disorders29–31	Individually rare clinical heterogeneity Receptor defects Autosomal recessive Other platelet defects Autosomal dominant	Prevalence of Bernard–Soulier syndrome and Glanzmann thrombasthenia 1/1 000 000 Decreased or absent platelet surface receptors 6 conditions: ♦ Bernard–Soulier syndrome ♦ Glanzmann thrombasthenia ♦ Platelet type von Willebrand ♦ ADP receptor ♦ Thromboxane A2 receptor ♦ Glycoprotein VI deficiency Aberrant secretion (impaired adherence to vascular endothelium) or altered signalling between platelets (impairing aggregation with other platelets)	Platelet count normal Prolonged bleeding time or closure time Abnormal results of specific platelet function assay Platelet function testing is not well standardized
Rare coagulation factor deficiencies	Autosomal recessive Autosomal recessive Autosomal recessive Autosomal recessive	Factor VII (chromosome 13q34) Factor X (chromosome 13q34) Factor V (chromosome 1q24.2) Factor II (chromosome 11p11-p12)	Low fibrinogen level Deficiency levels of specific factor(s)
α2-antiplasmin deficiency32	Rare, but prevalence increased with consanguinity		Low α2-antiplasmin level aPTT and INR normal

ADP = adenosine diphosphate; aPTT = activated partial thromboplastin time; INR = International Normalized Ratio; vWF = von Willebrand factor.