Autosomal recessive inherited bleeding disorders in Pakistan: a cross-sectional study from selected regions

Arshi Naz,Ikram Din Ujjan,Fazle Raziq,Samina Amanat,Muhammad Younus Jamal,Tahir Sultan Shamsi,Ayisha Imran,Akber Najmuddin,Humayun Patel,Nisar Ahmed

doi:10.1186/s13023-017-0620-6

Abstract

BackgroundAutosomal recessive bleeding disorders (ARBDs) include deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K dependent clotting factors, combined factor V & VIII, Von Willebrand Disease (vWD) type 3, Glanzmann’s thrombasthenia (GT) and Bernard–Soulier syndrome. Patients with primary bleeding disorders from all the major provincial capitals of Pakistan were screened for ARBDs. Prothrombin (PT), activated partial thromboplastin time (APTT), bleeding time (BT) and fibrinogen levels were measured. Cases with isolated prolonged APTT were tested for factors VIII and IX using factor assays This was followed by FXI:C level assessment in cases with normal FVIII and FIX levels. vWD was screened in patients with low FVIII levels. Factors II, V and X were tested in patients with simultaneous prolongation of PT and APTT. Peripheral blood film examination and platelet aggregation studies were performed to assess platelet disorders. Urea clot solubility testing was done to detect Factor XIII levels where platelet function tests were normal. Descriptive analysis was done using SPSS version 16.ResultsOf the 429 suspected bleeding disorder patients, 148 (35%) were diagnosed with hemophilia A and 211 (49.1%) patients had ARBDs. 70 patients (16.3%) remained undiagnosed. Out of 211 patients with ARBD; 95 (33.8%) had vWD type 3. Fibrinogen deficiency was found in 34 patients (12%), GT in 27 (9.6%), factor XIII deficiency in 13 (4.6%), factor VII deficiency in 12 (4.3%), factor V deficiency in 9 (3.2%). Eight patients (2.8%) had vitamin K-dependent clotting factor deficiency, Bernard–Soulier syndrome was diagnosed in seven patients (2.5%), factor X deficiency in 2 (0.7%), factor II deficiency in 2 (0.7%), factor XI deficiency and combined factor V and VIII deficiency in 1 (0.4%) patient each.ConclusionvWD type 3 was the most common ARBD found in our sample of patients in Pakistan, followed by fibrinogen deficiency and GT in respective order.

Highlights

Autosomal recessive bleeding disorders (ARBDs) include deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K dependent clotting factors, combined factor V & VIII, Von Willebrand Disease type 3, Glanzmann’s thrombasthenia (GT) and Bernard–Soulier syndrome
Fibrinogen deficiency has a prevalence of 1 in a million [14, 15]. It is subdivided into two distinct phenotypes: quantitative defect and qualitative defect, Prothrombin deficiency (PD) has a prevalence of approximately 1 in two million [16] and has two phenotypes: true hypoprothrombinemia and dysprothrombinemia [16]
Combined deficiency of factor V and VIII is associated with mutations in the LMAN1 and MCFD2 genes [20, 21]

Summary

Introduction

Autosomal recessive bleeding disorders (ARBDs) include deficiencies of clotting factors I, II, V, VII, X, XI, XIII, vitamin K dependent clotting factors, combined factor V & VIII, Von Willebrand Disease (vWD) type 3, Glanzmann’s thrombasthenia (GT) and Bernard–Soulier syndrome. 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). 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]. Platelets from patients with BSS lack the major surface membrane glycoprotein complex, glycoprotein (GP) Ib-IX-V [31]

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