Frequency, clinical, and laboratory findings of platelet secretion disorders in patients referred to the specialized coagulation laboratory of the Iranian Blood Transfusion Organization.

OBJECTIVES: Platelet secretion disorders (PSDs) are a subgroup of platelet function disorders (PFDs) caused by defects in the content or release of platelet granules. These patients have a variable degree of mucocutaneous bleeding tendency. The diagnostic facilities of PSDs are imitated in Iran, even in specialized coagulation laboratories. The present study aims to estimate the frequency of PSDs among patients referred to the Iranian Blood Transfusion Organization (IBTO). METHODS: The research population includes all patients referred to the specialized coagulation laboratory of IBTO and requested platelet function and von Willebrand testing by their physicians. They were recruited between May 2022 and October 2022 if they were not diagnosed as having procoagulant defects, von Willebrand disease (VWD), Glanzmann thrombasthenia (GT), Bernard-Soulier syndrome (BSS), and platelet count <100 × 10 9 (except in the syndromic forms). Patients with a defect in response to at least two agonists in Light transmission aggregometry (LTA), one agonist in the ATP-secretion study, and/or impairment in the expression of CD62P are considered PSDs. RESULTS: Among 121 cases referred to our center over 6 months, 40 patients fulfilled the inclusion and exclusion criteria. Ten patients were diagnosed with PSDs. Six were classified as δ-platelet secretion disorders (δ-PSD), two α-platelet secretion disorders (α-PSD), and two αδ-platelet secretion disorders (αδ-PSD). CONCLUSIONS: The prevalence of PSDs in our population study was 25% (10/40), which seems highly prevalent. Therefore, expanding laboratory approaches to platelet function defects is necessary as a routine in our country.

Utility of the international society on thrombosis and hemostasis-bleeding assessment tool in the diagnosis of patients who suspected of platelet function disorders.

The ISTH-BAT is a structured bleeding assessment tool to record and help diagnose patients with possible bleeding disorders. However, a few studies evaluated the utility of ISTH-BAT in diagnosing patients with platelet function defects (PFDs). In this study, we evaluated the diagnostic utility of ISTH-BAT in predicting PFDs among patients suspected of PFDs. Forty patients suspected of PFDs and 21 normal healthy controls were evaluated by the ISTH-BAT scoring system, light transmission aggregometry (LTA), ATP-releasing assays (lumi-aggregometry), and expression of CD62P for diagnosis of PFDs. Among 40 patients suspected of PFDs, 10 were diagnosed as PFDs using lumiaggregometry and CD62P. The ISTH-BAT score in patients suspected of PFDs [(6, interquartile range (IQR) 1-8] and patients with PFDs was significantly higher than the control group (0; IQR 0-0) ( P  < 0.001). Receiver operating characteristic curves indicate that ISTH-BAT is not able to discriminate patients with PFDs from those without PFDs (areas under the curve of 0.620 (95% confidence interval 0.415-0.825). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ISTH-BAT in predicting the presence of PFDs, respectively, were 40, 73.3, 33.3, and 78.6% in the cut-off ISTH-BAT at least 4 in adult men, at least 6 in adult women, and at least 3 in children (age < 18). The ISTH-BAT scoring system has good discriminatory power in diagnosing patients with PFDs from healthy controls but is ineffective in differentiating them from those without PFDs.

von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

BACKGROUND: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions. OBJECTIVE: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS. METHODS: An indirect in-house enzyme-linked immunosorbent assay has been used to test all the alloantibodies against VWF. Neutralizing antibodies (inhibitors) have been tested with a Bethesda-based method by using a VWF collagen binding (VWF:CB) assay. Samples positive for anti-VWF antibodies were further tested with Bethesda-based methods by using the semiautomated gain-of-function glycoprotein-Ib binding (VWF:GPIbM) and a VWF antigen (VWF:Ag) enzyme-linked immunosorbent assay. RESULTS: In total, 18 of the 213 (8.4%) subjects tested positive for anti-VWF antibodies and 13 of 213 (6%) had VWF:CB inhibitors. These 13 were among the 18 with anti-VWF antibodies. Of the 5 without VWF:CB inhibitors, 3 had non-neutralizing antibodies, 1 only inhibitor against VWF:GPIbM, and one could not be tested further. Ten of the 13 subjects with VWF:CB inhibitors also had VWF:GPIbM inhibitors, 6 of whom also had VWF:Ag inhibitors. Subjects with inhibitors were homozygous for VWF null alleles (11/14), homozygous for a missense variant (1/14), or partially characterized (2/14). CONCLUSIONS: Anti-VWF antibodies were found in 8.4% of subjects with type 3 VWD, whereas neutralizing VWF inhibitors were found in 6%, mainly in subjects homozygous for VWF null alleles. Because inhibitors may be directed toward different VWF epitopes, their detection is dependent on the assay used.

Von Willebrand factor propeptide and pathophysiological mechanisms in European and Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study.

BACKGROUND: Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. OBJECTIVE: To investigate whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated with bleeding severity. METHODS: European and Iranian type 3 patients were enrolled in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney test. Median differences with 95% confidence intervals (CI) were estimated using the Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using Spearman's rank correlation. RESULTS: Homozygosity/compound heterozygosity for missense variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7; P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII: C/VWF:Ag ratio was similarly increased in both. VWFpp level did not correlate with the bleeding symptoms (r = .024; P = .778). CONCLUSIONS: An increased VWFpp/VWF:Ag ratio is indicative of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense from null alleles. The VWFpp level was not associated with the severity of bleeding phenotype.

Isolation of the Anticoagulant and Procoagulant Fractions of the Venom of Iranian Endemic Echis carinatus.

Background: The venom of Echis carinatus contains both procoagulant and anticoagulant components that can either promote or block the blood coagulation cascade, and some of these components affect platelet function in different ways. Objectives: The present study focuses on setting up a procedure for the purification of crude venom and designing appropriate clotting tests in order to characterize the procoagulant and anticoagulant fractions of E. carinatus venom. Methods: Chromatographic methods, including gel filtration, ion-exchange chromatography, and reverse-phase high-performance liquid chromatography (HPLC), were applied for purifying these fractions. Coagulant activity testing, prothrombin time (PT), and activated partial thromboplastin time (APTT) were used to determine procoagulant and anticoagulant properties. For measuring molecular weight, 15% SDS-PAGE electrophoresis with a molecular weight standard ranging from 6.5 to 200 kDa was used. Results: We obtained five fractions named F1, F2, F3, F4, and F5. The F1 and F2 fractions showed procoagulant activity, and the F5 fraction had anticoagulant activity. The molecular weight of F2.4.2 from fraction F2 and F5.1 from fraction F5 were analyzed by SDS-PAGE electrophoresis under the reducing condition. These factors were identified as a single protein band at the end of purification. The molecular weights of these purified fractions were estimated to be 7.5 kDa and 38 kDa for F5.1(b) and F2.4.2(b), respectively. Conclusions: Our findings suggest an efficient and suitable procedure for the identification and purification of the procoagulant and anticoagulant factors of the venom of Iranian E. carinatus using the PT and APTT assays.

Homozygous SOD1 Variation L144S Produces a Severe Form of Amyotrophic Lateral Sclerosis in an Iranian Family.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by degeneration of motor neurons determining progressive muscular atrophy, weakness, and death from respiratory failure. METHODS: Here, we report clinical and molecular findings of a novel Iranian family affected with a severe form of early-onset familial ALS. RESULTS: Three siblings born to consanguineous parents developed a form of ALS characterized by early-onset lower limb involvement and a fast progression, proving fatal at age 16 years for 1 of them. Molecular analysis of the SOD1 gene revealed the homozygous substitution c.434T>C in exon 5 resulting in the amino acid change p.Leu144Ser (L144S), previously reported as a dominant variant. Both parents were heterozygous carriers. The probands' mother recently developed a late-onset ALS with predominant upper motor neuron involvement. DISCUSSION: This report adds p.L144S to the short list of homozygous SOD1 variants and suggests that the development of an earlier-onset and/or faster disease progression can occur when 2 mutated alleles are present.

The activity of labile coagulation factors and fibrinogen in thawed plasma during a 5 day storage period in the hospital blood bank refrigerator.

BACKGROUND: Fresh frozen plasma (FFP) is used to treat coagulation disorders. Even though the activity of labile coagulation factors gradually decreases once thawed, it can be used up to 24 h after thawing, if stored properly. In this study, the level of coagulation factor activity was evaluated in thawed plasma during a 5 day storage period. MATERIALS AND METHODS: This cross-sectional study was performed on 40 FFP units prepared in Yazd Blood Center. Samples were thawed in a waterbath for 20-30 min at 30-37°C and then stored in the hospital blood bank refrigerator. The level of fibrinogen concentration, as a stable factor and, coagulation factors V and VIII, as labile factors, were measured in the plasma immediately following the thawing process as well as 24 and 120 h after the process. Data analysis was performed using SPSS software 20. RESULTS: The fibrinogen level remained stable for up to 24 h after thawing; after 120 h there was a 1.66% decrease with the mean level of 334.0 ± 53.3 mg/dl. The mean activity of factors V and VIII levels decreased by 12.3%, and 26% respectively over 120 h after thawing when compared to that after 24 h. A 120 h after thawing Factor V activity was above 70% in 87.5% of thawed plasmas and its mean activity was 81.6 ± 11.8. Factor VIII activity was above 70% in only 35% of thawed plasmas with the mean activity of 64.4 ± 17.2. CONCLUSION: Thawed plasma can be used for up to 5 days in all therapeutic applications of FFP since it still has the essential hemostatic effects. However, in situations where higher levels of FVIII are needed, Thawed Plasma is not a suitable alternative. In such cases FFP, FVIII concentrate or cryoprecipitated antihemophilic factor should be used.

Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

Type 3 von Willebrand disease (VWD3) is a rare and severe bleeding disorder characterized by often undetectable von Willebrand factor (VWF) plasma levels, a recessive inheritance pattern, and heterogeneous genotype. The objective of this study was to identify the VWF defects in 265 European and Iranian patients with VWD3 enrolled in 3WINTERS-IPS (Type 3 Von Willebrand International Registries Inhibitor Prospective Study). All analyses were performed in centralized laboratories. The VWF genotype was studied in 231 patients with available DNA (121 [115 families] from Europe [EU], and 110 [91 families] from Iran [IR]). Among 206 unrelated patients, 134 were homozygous (EU/IR = 57/77) and 50 were compound heterozygous (EU/IR = 43/7) for VWF variants. In 22 patients, no or only one variant was found. A total of 154 different VWF variants (EU/IR = 101/58 [5 shared]) were identified among the 379 affected alleles (EU/IR = 210/169), of which 48 (EU/IR = 18/30) were novel. The variants p.Arg1659*, p.Arg1853*, p.Arg2535*, p.Cys275Ser, and delEx1_Ex5 were found in both European and Iranian VWD3 patients. Sixty variants were identified only in a single allele (EU/IR = 50/10), whereas 18 were recurrent (≥3 patients) within 144 affected alleles. Nine large deletions and one large insertion were found. Although most variants predicted null alleles, 21% of patients carried at least 1 missense variant. VWD3 genotype was more heterogeneous in the European population than in the Iranian population, with nearly twice as many different variants. A higher number of novel variants were found in the Iranian VWD3 patients.

Genetic analysis of non-severe hemophilia A phenotype with A discrepancy between one-stage and chromogenic factor VIII activity assays.

INTRODUCTION: The diagnosis of hemophilia A (HA) is based on the measurement of factor VIII activity (VIII:C). About one-third of non-severe HA patients show a discrepancy of VIII:C measured by one-stage (VIII:C 1st) and chromogenic (VIII:C chr) assays. Different mutations in the F8 gene may cause the discrepancy in results of the FVIII activity assay. The aim of this study was to investigate F8 gene mutations in patients with assay discrepancies and to evaluate their impact on the results of VIII:C assays. METHODS: Mutation analysis was performed on 41 individuals with a discrepancy in VIII:C 1st and FVIII: C chr assays by direct sequencing. In addition, the effect of the variants on FVIII macromolecule structure was investigated by in silico and bioinformatics tools. RESULTS: Genetic analysis disclosed 22 different variants, of which 19 were identified for the first time to be involved in the phenotype of VIII:C discrepancy. Most of the variants related to the higher VIII:C 1st were found in A1, A2, A3 domains. The variant related to VIII:C chr > VIII:C 1st was located in the thrombin cleavage site. In silico analysis showed the effect of variants on FVIII macromolecule stability, which may be the possible mechanism causing the discrepancy. CONCLUSION: Our data shed light on the impact of genetic defects on VIII:C assay and provided evidence that the consideration of these mutations may open a new window to the proper diagnosis and treatment monitoring of non-severe HA patients.

Severe Prekallikrein Deficiency Associated with Low Level of Factor XII: A Case Report.

Hereditary deficiency of plasma prekallikrein (PPK) is a rare autosomal recessive disease. The affected patients are often asymptomatic and diagnosed incidentally during preoperative investigations or during hospitalization by isolated prolongation of activated partial thromboplastin time (aPTT). In this article, we report, a 46-year-old woman who was candidate for two invasive procedures (thyroid FNA and hysterectomy) and underwent preoperative evaluation. Due to prolonged aPTT with normal PT she was referred to the IBTO reference coagulation laboratory for specific coagulation assays. Ultimately, the examinations revealed severe PPK deficiency (<1%) with partial deficiency of factor XII level (25%).

Von Willebrand disease combined with coagulation defects in Iran.

BACKGROUND: Although Von Willebrand disease (VWD) is the most common inherited bleeding disorder, few cases of VWD combined with coagulation defects have been reported. This study sought to determine the clinical and laboratory features of VWD combined with other coagulation defects and to evaluate the prevalence of this combination in Iran. MATERIAL AND METHODS: A total of 3,120 cases were evaluated to confirm a suspected diagnosis of VWD. Clinical and laboratory phenotypes, including bleeding scores (BS), were also obtained. RESULTS: A diagnosis of VWD was established for 130 patients. Following their further characterisation, a subgroup of 25 patients with a dual or triple combination of VWD with coagulation defects (FXII, FXI, FIX, FVII, FV, and lupus anticoagulant) was identified. Their laboratory and clinical data were compared with those of healthy controls (n=25) and VWD-only patients (n=25). No differences were observed for VWF-related laboratory measurements between the combined deficient cases and those with VWD only, results being expectedly lower than in healthy controls. The median BS of combined patients was 4, higher than for VWD-only and control groups (median BS 3 and 1; p=0.55 and p<0.001, respectively). DISCUSSION: The prevalence of combined coagulation defects was 19.2% among all the VWD cases. The co-occurrence of VWD with clotting factor deficiencies may lead to more severe clinical presentations. To ensure adequate treatment, combined defects should be considered in VWD patients presenting with a more severe bleeding phenotype than expected or with a poor response to treatment.

Heparin-Induced Thrombocytopenia in Iranian Cardiac Surgery Patients Using the 4Ts Clinical Scoring System and Laboratory Methods.

Background: Heparin-induced thrombocytopenia (HIT) is a serious adverse drug reaction. HIT diagnosis needs an algorithmic approach including clinical evaluation and laboratory tests (screening and confirmatory). Few studies have been conducted on HIT in Iran, and most existing research has been general and based on clinical evaluations alone. The present study was conducted to determine the prevalence of HIT among cardiac surgery patients using an algorithmic approach. Materials and Methods: A cross-sectional study was carried out over a period of 10 months, at Modares Hospital (Tehran, Iran) on 92 patients who were candidates for cardiac surgery. For the clinical evaluation, the 4Ts scoring system was used; in cases with 4Ts scores ≥4, a laboratory evaluation of anti-PF4/heparin antibody (Ab) was performed by enzyme-linked immunosorbent assay (ELISA) and a HIPA test too as a functional confirmatory method. The patients with 4Ts scores ≥4 who were ELISA positive (OD ≥0.2) and HIPA positive were taken as a definite case of HIT. Results: Of the 92 patients who had undergone cardiac surgery, 14 (15%) had 4Ts scores ≥4. Anti- PF4/heparin Ab was detected in eight patients using the ELISA and in six patients using the HIPA. Ultimately, definite HIT was confirmed in five of the patients. Conclusion: The prevalence of HIT was 5.4% among the cardiac surgery patients assessed in the present study. To the researchers' knowledge, this is the first time that HIT has been evaluated in Iran using a comprehensive algorithmic approach including clinical history-taking and both immunological and functional laboratory tests, and the findings showed a slightly higher HIT frequency in this single-center study in comparison with the other studies carried out in other countries.

Discrepancy between the results of one-stage and chromogenic factor VIII: C assays in patients with mild/moderate hemophilia A.

: Diagnosis of hemophilia A is generally based on the measurement of plasma factor VIII activity (FVIII:C) using the one-stage assay (OSA) or the two-stage chromogenic substrate assay (CSA). The results of these methods show considerable discrepancy in about one-third of non-severe hemophilia A patients. The aim of this study was to assess the prevalence of FVIII:C assay discrepancy in non-severe hemophilia A patients in Iran and the relationship between the bleeding tendency with the level of FVIII:C by each method. Patients registered as mild or moderate hemophilia A in hemophilia clinic of Imam Khomeini Hospital were included. In each patient, FVIII:C level was assessed using one-stage (FVIII:C1) and chromogenic (FVIII:CR) methods. Assay discrepancy was defined as a two-fold or greater difference between the results of two assays. Bleeding tendency of the patients was recorded based on 'ISTH-BAT'. Sixty male patients were eligible for the study. The levels of FVIII:C1 was higher than FVIII:CR in 90% of patients. Assay discrepancy was seen in 41 (68%) patients. The classification of hemophilia A in 23 (38%) patients was modified by chromogenic method. No significant correlation was noted between the results of ISTH BAT with FVIII:C levels of each method. Regarding the prevalence of FVIII:C assay discrepancy in 2/3 of our non-severe hemophilia A patients, high rate of disease severity modification by chromogenic method and no significant relation between the clinical bleeding phenotype with any method, the authors highly recommend to perform both FVIII:C assays for the diagnosis and classification of non-severe hemophilia A.

Are Iranian patients with von Willebrand disease type 2N properly differentiated from hemophilia A and do they receive appropriate treatment?

: The defect function of the von Willebrand factor (VWF) in carrying factor VIII (FVIII) leads to von Willebrand disease type 2N (VWD 2N) which could be easily misdiagnosed as hemophilia A. Differentiating of VWD 2N from hemophilia A is crucial for patient treatment and genetic counseling. As a retrospective study, we aimed to evaluate the current diagnostic work-up of Iranian patients with mild/moderate deficiency of FVIII levels and the possibility of misdiagnosis of VWD 2N as hemophilia A. All patients who referred to the reference coagulation laboratory at the Iranian Blood Transfusion Organization in a 10-months period for bleeding diathesis work-up with the request of FVIII activity level were included. Clinical and laboratory phenotypes including International Society on Thrombosis and Hemostasis - Bleeding Assessment Tool, FVIII activity, VWF antigen, VWF ristocetin cofactor, and FVIII binding capacity of VWF were assessed on suspected cases for VWD 2N. In total, the results of 896 patients for investigation of VWD 2N were evaluated and five new patients were identified within unrelated families with abnormal VWF:FVIIIB levels. Four were heterozygous for VWD 2N and one homozygous whom all were misdiagnosed as hemophilia A and underwent inappropriate treatments. The median bleeding score of the VWD 2N population was nine (4-13). In Iran, probably a significant number of VWD 2N patients are misdiagnosed as hemophilia A due to insufficient test panel for subtyping of von Willebrand disease. This study also emphasized the need for inclusion of the VWF:FVIIIB in suspected hemophilia A to achieve an optimal treatment strategy.

Procoagulant Activity of Red Blood Cell-Derived Microvesicles during Red Cell Storage.

BACKGROUND: Red blood cells (RBCs) undergo structural and biochemical alterations during storage which are collectively called RBC storage lesion and cause a decrease in RBC recovery and survival. During storage, erythrocytes release an increasing number of microvesicles (MVs) that have key roles in biological processes. We aimed to investigate the procoagulant activity (PCA) of RBC-derived MVs during storage. METHODS: 20 packed RBCs were stored for up to 42 days. Samples were taken at seven different times and evaluated for the presence of RBC-MVs. MVs were separated, and following filtration flow cytometry was used to characterize RBC-MVs based on the expression of glycophorin A (Gly.A) and annexin V (AnnV) antigens. The coagulant activity of RBC-MVs was tested by clotting time (CT) and PCA assays. Results were compared before and after filtration. RESULTS: Flow cytometry revealed a 17.6-fold increase in RBC-MVs after 6 weeks of storage. Significant correlations were found between AnnV+ MVs and PCA (r = 0.96; p < 0.001), and CT (r = -0.77; p < 0.001) which was associated with increased PCA and shortened CT with RBC aging. Filtration of samples efficiently removed MVs (p < 0.001) and also reduced in vitro PCA of MVs (p < 0.001). CONCLUSION: RBC-MVs are procoagulant (particularly AnnV+ MVs) Reduction of MVs from RBC concentrates may reduce the risk of transfusion-induced thrombotic complications.

Correlation of bleeding score with frequency and severity of bleeding symptoms in FXIII deficiency assessing by the ISTH Bleeding Assessment Tool.

OBJECTIVES: The ISTH bleeding assessment tool (ISTH-BAT) is developed for standardization of bleeding symptoms in bleeding disorders. The aim of this study is to apply this bleeding score for FXIII deficient patients and its relation to the frequency and severity of symptoms. METHODS: In this cross-sectional study, 63 patients with severe FXIII deficiency were evaluated for the assessment of bleeding score according to the standard ISTH-BAT questionnaire. All patients were registered at two major thrombosis and hemostasis centers in Iran affiliated to Zahedan University of medical sciences (50 patients) and Shiraz University of medical sciences (13 patients). RESULTS: Significant correlations between the bleeding score and number of symptoms (r = 0.668, P < 0.001) and with a number of severe symptoms (r = 0.938, P < 0.001) were detected. There was no significant relationship between the mean bleeding score and CNS bleeding (P = 0.390). CONCLUSION: The ISTH-BAT score is an acceptable bleeding assessment tool for standardization and evaluation of patients with FXIII deficiency.

Comparative evaluation of the safety and efficacy of recombinant FVIII in severe hemophilia A patients.

OBJECTIVE: This study compared the safety and efficacy of Safacto® versus xyntha® in patients with severe hemophilia A. METHODS: Thirty-three male patients with severe hemophilia A were randomly divided into two groups. Seventeen patients received Safacto® and 16 patients received Xyntha® for four consecutive times. The dosage of FVIII was 40-50 IU/kg for each injection. Plasma level of FVIII activity was evaluated before every injection, 15 minutes after the injection and one month after the start of the trial. The rate of factor VIII activity, pain and joint motion were also assessed before and after the treatment. RESULTS: Plasma level of FVIII clotting activity in Safacto® and Xyntha® were 1.96±0.5 IU/dl and 1.63±0.5 IU/dl and increased to 88.84±25.2 IU/dl and 100.09±17.8 IU/dl, respectively (P<0.001). Pain score and range of motion improvement were 9.3±0.9 and 8.7±0.1 in Safacto® (P=0.17); and 9.4±0.8 and 8.8±0.3 in Xyntha® (P=0.35), respectively. No allergic or other unfavorable reactions was observed with either of the preparations. CONCLUSION: This study showed that Safacto® has a favorable efficacy and safety profile.

Long-term prophylaxis in patients with severe congenital factor XIII deficiency is not complicated by inhibitor formation.

: Congenital factor XIII (FXIII) deficiency is a rare bleeding disorder accompanied by a variety of bleeding events. Severely deficient patients require regular replacement therapy. With development of FXIII concentrate, the risk of viral infections transmitted by fresh frozen plasma and cryoprecipitate is diminished, but the possibility of inhibitor development remains a challenging issue in the management of these patients. The aim of this study was to assess FXIII inhibitor development in Iranian patients with FXIII deficiency (FXIIID). This study enrolled 50 (30 women and 20 men) patients with severe congenital FXIIID from southeast Iran who underwent long-term (more than 4 years or more than 50 injections) prophylaxis with FXIII concentrate (Fibrogammin P, Dade Behring, Marburg, Germany). We evaluated plasma FXIII activity and FXIII inhibitor on day 28 after the last prophylaxis administration. The method for investigation of FXIII inhibitor was based on Bethesda assay. The mean age of the study population was 13.8 ±â€Š8.3 years. The minimum and maximum FXIII activity levels were less than 1-4.5% (mean ±â€ŠSD, 2.6 ±â€Š0.7%). Our investigations showed that all patients with severe form of FXIIID were treated without inciting inhibitor development. Despite long-term prophylaxis in the studied patients, none was found to have developed FXIII inhibitors.

Evaluation of Aggregometery Parameters and Efficacy of Plavix versus Clopidex in Patients Suffering from Ischemic Heart Disease: A Randomized Double Blind Clinical Trial.

BACKGROUND: Ischemic heart disease is the leading cause of death in most societies. In a pathophysiologic point of view, it chiefly results from the formation of thrombus in coronary arteries which could not be only prevented by aspirin. Many of clinical trials have shown the long-term benefits of antiplatelet drugs in reducing the risk of thrombotic accidents. OBJECTIVES: Clopidogrel is a thienopyridine derivative used to prevent platelets from adhering together by direct inhibition of Adenosine diphosphate (ADP), the major factor behind platelets aggregation. Sanofi-Aventis and Bristol-Myers are companies that produce Clopidogrel by the name of Clopidogrel bisulfate. Its trade name is Plavix, nonetheless in Iran it is distributed under the name of Clopidex by Exir Company. In this study we are to compare Plavix and Clopidex in terms of efficacy as well as aggregometry parameters like ADP and PRP (Platelet Rich Plasma). PATIENTS AND METHODS: This is a double blind clinical trial in which we had two groups of patients suffering from Ischemic heart disease who were selected by inclusion criteria. Group A (36 patients) took Plavix (75 mg/d) and group B (36 patients) used clopidex (75 mg/d) both for 30 days. The aggregometry parameters also consisted of PRP and ADP that were run on the patients before and after the study. Finally, a comparison of aforementioned tests, quality of life, lab parameters and compliance in both groups was provided. RESULTS: In groups A and B, the mean levels of PRP before the study were 348000 and 340000/µL respectively. The ADPs were also 73/76 and 68/07 µM that showed no significant difference (P > 0.05).The Means of ADP5 in group A before and after the study were 66.40 and 43.84 µM respectively that there was significant difference (P = 0.001). The Means of ADP5 in group B before and after the study were 58.04 and 40.16 µM respectively that there was significant difference (P < 0.001).The Means of ADP20 in group A before and after the study were 73.76 and 54.97 µM respectively which showed significant difference (P < 0.001). The Means of ADP20 in group B before and after the study were 68.07 and 52.49 µM respectively which showed significant difference (P = 0.001). Difference of ADP5 between group A and B was not significant (P = 0.495). Difference of ADP20 between group A and B was not significant (P = 0.721). The Means of PRP in group A before and after the study were 348000 and 335000/ µL respectively that there was no significant difference (P = 0.66). The Means of PRP in group B before and after the study were 340000 and 336000/ µL respectively that indicated no significant difference (P = 0.81). Difference of PRP between group A and B was not significant (P = 0.563). CONCLUSIONS: Our findings suggested that both drugs significantly lessen the ADP level; even so there was no significant difference between two groups in PRP and ADP factors.