The incidence of autosomal recessive bleeding disorders (ARBDs) worldwide is uncommon at about 3–5% [
1,
2] as compared with other causes of bleeding. However, these disorders predominate in those regions of the world where consanguineous marriages are encouraged [
3]. Pakistan has a high rate of such marriages [
4,
5]. The prevalence of some of these disorders in the local population has only been reported in a few studies [
6‐
11] and a lack of diagnostic facilities and expertise has prevented a comprehensive study to identify ARBDs.
The ARBDs include deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K-dependent clotting factors [VKDCF; II, VII, IX and X], combined factors V and VIII, von Willebrand disease type 3 (vWD), Glanzmann’s thrombasthenia (GT) and Bernard–Soulier syndrome (BSS). The presentation and bleeding pattern in these patients varies according to the etiology of each disorder [
12,
13]. Life threatening bleeding episodes e.g., central nervous system or musculoskeletal bleeding, occur rarely.
Fibrinogen deficiency has a prevalence of 1 in a million [
14,
15]. It is subdivided into two distinct phenotypes: quantitative defect (afibrinogenemia and hypofibrinogenemia) and qualitative defect (dysfibrinogenemia and hypodysfibrinogenemia), Prothrombin deficiency (PD) has a prevalence of approximately 1 in two million [
16] and has two phenotypes: true hypoprothrombinemia (type I deficiency) and dysprothrombinemia (type II deficiency) [
16]. Factor V [FV] deficiency is manifested by skin and mucus membrane bleeding, epistaxis and menorrhagia. Prevalence is 1 in a million [
17]. Factor VII deficiency presents as a hemophilia-like bleeding disorder with an estimated prevalence of 1 in 300,000–500,000 [
18]. The most severe form of vWD is type 3, characterized by a bleeding disorder associated with a total or near-total absence of von Willebrand factor (vWF) with deficiency of plasmatic factor VIII (FVIII) [
8]. The type 3 vW disease is the rarest form of vWD, accounting for less than 5% of all cases of bleeding disorders worldwide. Annual incidence ranges from 1 in two million to 1 in 350,000 in Europe and the United States, with estimates of around 1 per 500,000 in countries where consanguinity is more frequent [
19]. Combined deficiency of factor V and VIII is associated with mutations in the LMAN1 and MCFD2 genes [
20,
21]. It is characterized by concomitantly low levels (usually between 5 and 20%) of both FV and FVIII and is associated with a mild to moderate bleeding tendency [
22]. There are two variants to vitamin K-dependent clotting factor deficiency VKDCF; VKDCF1, associated with point mutations in the gamma-glutamyl carboxylase gene (GGCX), and VKDCF2, which results from point mutations in the vitamin K epoxide reductase gene (VKORC1) [
23]. Factor X deficiency has an estimated prevalence of 1 in one million individuals [
24]. Factor XI deficiency can manifest first as a bleeding disorder or as an incidental laboratory abnormality. Occurrence is approximately 1 per one million [
25]. Factor XIII deficiency is a rare disorder, causing a severe bleeding tendency. The incidence is 1 per one million to 1 in five million people [
26,
27]. GT is the most frequently diagnosed inherited disorder of platelet function (prevalence, 1 in a million) [
28]. Patients lack or have nonfunctional alpha 2b beta 3 (αIIbβ3) integrin. Type I individuals have <5% of αIIbβ3, while type II have between 10 and 20%. In type III, there are normal levels of αIIbβ3, but they are not functional [
29]. The autosomal recessive disorder BSS has a prevalence of 1 in one million [
30]. Platelets from patients with BSS lack the major surface membrane glycoprotein complex, glycoprotein (GP) Ib-IX-V [
31].
The aim of this study was to determine and compare the 12 year period prevalence of ARBDs in several regions of Pakistan.