Population statistics show that one out of every 3 individuals in developed countries dies of thrombosis from one of its many forms (stroke, myocardial infarction, pulmonary embolism, and so forth). It is also clear that some individuals harbor one or more abnormalities that predispose them to thrombotic events, the so-called hypercoagulable state. Patients with a tendency to thrombosis are defined as having thrombophilia, and the term inherited thrombophilia is applied to individuals with predisposing genetic defect. A growing number of genetic abnormalities have been identified to predispose patients to venous thromboembolic disease, which is a common disorder associated with significant mortality and morbidity. Prior to 1993, the diagnosis of a hereditary disorder could be established in approximately 15% of patients under age 50. An extensive range of published literature now exists on the role of heritable thrombophilia. Antithrombin (AT), protein C and protein S are the major naturally occurring inhibitors of coagulation. Deficiencies of these proteins are relatively uncommon in the general population, the prevalence of heterozygous deficiencies is estimated at 10-20%.
Activated protein C resistance (APCR) secondary to the Factor V Leiden (FVL) mutation is more common, occurring in 2-15% of Caucasian population and 20-50% of adults with a first episode of venous thromboembolism (VTE). Similarly, the prothrombin mutation (PT 20210A), which results in increased levels of prothrombin has a prevalence of approximately 2% in the normal Caucasian population and 6% in unselected adults with VTE. The advances made in understanding the complexity of the hemostatic process as well as the availability of newer, more sophisticated tests have made it possible to diagnose and possibly prevent so-called idiopathic venous thromboembolism (VTE).
[See: Kuwait > Al Sayegh et al., 2009].
[See: Kuwait > Mohanty et al., 1996].
Awidi et al. (1993) conducted a four-year prospective study on patients admitted or referred with thromboembolic disease to Jordan University Hospital or to the Thrombosis/Haemostasis Laboratory at the University of Jordan. There were a total of 217 patients (102 males and 115 females) with confirmed thromboembolic disease. A total of 49 patients (26 males and 23 females) fulfilled the criteria of hereditary thrombophilia. There were 17 cases of protein C deficiency (PC), 15 protein S deficiency (PS), 10 antithrombin III deficiency (ATIII), 3 dyfibrinogenemia, 2 heparin cofactor II deficiency, and 2 plasminogen defects. In this group most of the thrombosis was venous. A positive family history was obtained in 65.3% of patients with hereditary thrombophilia. Twenty-seven additional relatives with deficiency were identified upon family studies. The calculated prevalence of hereditary thrombophilia in Jordan is put at 1/25,000.
Eid (2002) studied 602 (265 female, 337 male) patients with suspected thrombosis, arterial or venous. The prevalence of hereditary deficiencies of antithrombin (AT), protein S (PS), and protein C (PC) were studied over a seven-year period (1993-2000). Activated protein C (APC-R) resistance subjects were studied over four years (1996-2000). The mean age was 30 years in females and 42 years in males. A diagnosis was established in 22.4% (n = 135) of the subjects (20.3% venous, 2.1% arterial). Protein C deficiency was found in 3.8%, protein S deficiency in 2.3% and antithrombin deficiency in 1.4% of the sample group. An APC-R problem was seen in 23.0% (n = 89) of the surveyed population. Out of the APC-R patients, 75.0% had the DNA analysis of a factor V Leiden mutation present. Of the subjects found to have the mutation 87.0% were heterozygous and 13.0% were homozygous.
[See also: Kuwait > Mohanty et al., 1996].
Mohanty et al. (1996) conducted a 4-year (1986-1990) retrospective study on 130 unrelated patients with recurrent deep venous thrombosis in order to determine the possible etiology. The study group consisted of only ethnic Arab patients from Kuwait, Palestine, Jordan, Egypt, Sudan, Iraq, and Syria. Fifteen patients were found to have hereditary protein C deficiency (11.52%). Family studies revealed autosomal recessive inheritance in one patient and a dominant pattern in the remaining 14 patients. Protein S deficiency was found in eight cases (6.1%), AT-III deficiency was established in five cases (3.8%) and a fibrinolytic defect in 33 cases (25.4%). Thrombosis of visceral and cerebral vessels and a positive family history were more frequently found among patients who had hereditary deficiency of one or the other antithrombotic factor. Thrombophlebitis of superficial veins was found to be very common in patients with protein C and protein S deficiency and virtually absent in AT-III deficiency.
Jadaon and Dashti (2005) conducted a study to determine the prevalence and the possible risk of a polymorphism in the factor V gene (named HR2) in Arabs. The study consisted of an Arabic cohort involving 188 Venous Thromboembolism (VTE) cases (94 were males and 94 were females) and 100 healthy subjects. The study resulted in 31 patients and seven healthy subjects having HR2 haplotype, with a prevalence of 16.5% and 7%, respectively. In addition, 43 subjects were found to have more than one risk factor for VTE. Jadaon and Dashti (2005) concluded that the prevalence of HR2 haplotype is high in Arabs, having a 2.62-fold greater risk of developing VTE. Furthermore, it was found that the coexistence of two or more genetic/acquired defects of VTE is rather frequent in Arab patients.
Al Sayegh et al. (2009) established a multicentre, prospective registry to identify consecutive patients with acute asymptomatic VTE from Bahrain, Kuwait, Oman, Qatar, and the United Arab Emirates. A total of 242 patients (128 men; average age: 49.8 years; average BMI: 27.75) with confirmed VTE were enrolled in the study during a 60-day period in 2003. Of these, 187 were diagnosed with isolated DVT, 35 with isolated PE (Pulmonary Embolism), and 20 with both DVT and PE. The majority of the cases originated from Kuwait (39.7%), followed by the UAE (33.5%), likely due to the larger number of participating centers in these countries. Interestingly, more than 40% of the cases originated from the medical wards. The most common symptoms in the case of patients with DVT were calf pain, calf swelling, localized tenderness, and warmth, whereas in cases with PE they were dyspnea, thoracic pain, cough, fever, and hypotension. DVT cases had, in the majority, proximal localization, while PE cases were localized segmentally in the lungs. DVT was diagnosed most commonly by ultrasound Doppler, followed by D-dimer test, while PE was diagnosed by lung scan, blood gas analysis, and/or D-dimer test. History of surgical intervention was revealed to be the biggest risk factor for development of VTE, with 80 of the patients having had a surgery in the one-year preceding their enrolment in the study; 83% having a VTE event within 4-weeks of the surgery. Other risk factors present included immobilization for more than three days, age more than 65 years, previous history of DVT or PE, and plaster cast/trauma. Patients with DVT were treated most commonly with low-molecular-weight heparin, and PE cases were treated with unfractionated heparin. Al Sayegh et al. (2009) recommended instituting an appropriate prophylaxis policy in the Gulf States to minimize VTE events among the high-risk group.
Al-Jaouni (2003) conducted a retrospective analysis in 179 consecutive Saudi patients (74 males, 105 females) that were screened between October 1997 and January 2002 at the King Abdul-Aziz University Hospital (KAUH) and King Fahd Armed Forces Hospital (KFAFH), Jeddah, Kingdom of Saudi Arabia. All patients had at least one of the following features: history of recurrent venous thromboembolism (VTE), first episode of unprovoked VTE, thrombosis in unusual site or thrombosis at young age with or without positive family history. Thrombotic workup included protein C, protein S, antithrombin (AT), APCR, prothrombin mutation, lupus anticoagulant (LA), and anticardiolipin (ACL). Functional assays were carried out in 179 patients. Molecular analysis of both FVL and prothrombin G20210A mutation was performed in 67 patients. Protein S deficiency was the most common, identified in 26/179 (14.5%) followed by protein C in 15/179 (8.4%), while AT was not deficient in all 179 tested patients. Activated protein C resistance was present in only 4 patients (2.2%). Two patients were tested positive for prothrombin mutation; one of them was heterozygous for FVL too. Eight percent of the patients had LA, while 4% had ACL antibodies.