CYP2C9 gene analysis of some Iranian hypersensitive patients to warfarin.

For the first time in this study, the pharmacogenetic effects of CYP2C9 polymorphism on warfarin sensitivity in some Iranian patients who are on warfarin treatment were shown. The study group consisted of clinically sensitive patients (21 patients) and the control group (37 adult patients). For detection of CYP2C9*2 and CYP2C9*3 variants, a protocol based on restriction fragment length polymorphism based polymerase chain reaction with Eco47I and KpnI was used. In clinically sensitive patients about 81% and in normal response patients about 24.3% carried variant genotypes.

Evaluation of rFVIIa (NovoSeven) in Glanzmann patients with thromboelastogram.

Glanzmann thrombasthenia (GT) is a rare platelet function disorder characterized by a defect in fibrinogen binding to platelet membrane glycoprotein (GP) IIb/IIIa. Recombinant FVIIa (rFVIIa) is a haemostatic agent approved for the treatment of haemophilia patients with inhibitors, patients with acquired haemophilia and in EU also for treatment of factor VII (FVII)-deficient patients and GT patients with antibodies to GPIIb-IIIa. The present study was conducted to evaluate the use of the whole blood test system, rotational thrombelastometry (ROTEM), in measuring the overall haemostasis potential of rFVIIa in 28 GT patients treated with rFVIIa. The correlation of administered rFVIIa and time to start fibrin formation and clot dynamic/stability was assessed and correlation to the clinical response was elucidated. Assessments were performed on predose blood samples spiked with four different concentrations of rFVIIa and whole blood samples taken at 10 and 120 min following dosing. ROTEM parameters clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) were measured. Both ex vivo and in vivo data showed beneficial effects on CT in the presence of rFVIIa, but no effect of added rFVIIa was seen on CFT and MCF. In conclusion, the use of thrombelastography at least in the modified form of ROTEM seems to be of limited use in predicting an adequate dose of rFVIIa in GT patients. A good clinical haemostatic response was recorded in spite of the limited changes in the ROTEM pattern supporting the conclusion that ROTEM should not be the method of choice for monitoring rFVIIa therapy in Glanzmann patients.

Pain affects health-related quality of life in kidney transplant recipients.

BACKGROUND: Chronic pain is prevalent in end-stage renal disease patients undergoing chronic hemodialysis. We do not fully know the intensity of chronic pain experienced by kidney recipients in comparison to those on chronic hemodialysis and healthy controls. Moreover, the effect of chronic pain on kidney recipients' health-related quality of life (HRQoL) is yet to be comprehensively addressed. We designed this study to find an answer to these questions. METHODS: In this case control study, we studied 205 kidney recipients, 69 hemodialysis patients, and 100 healthy controls, who were matched for age, sex, monthly family income, and educational level. The patients were evaluated for the intensity of chronic pain by Visual Analogue Scale (VAS). HRQoL was measured with Short Form 36 (SF-36) in the kidney recipients. Chronic pain intensity was compared in the study groups, and in the kidney recipients the correlation between SF-36 subscores and severity of pain was assessed. RESULTS: Severity of pain in the kidney recipients was lower than the hemodialysis patients, but more than the healthy controls (P=.001). The VAS pain score negatively correlated with the scores of SF- 36 total (r=-.329, P=01), mental health (r=-.190, P=07), physical health (r=-.275, P=.001), physical function (r=-.339, P=.001), role limitation due to physical problems (r=-.478, P=.001), role limitation due to emotional problems (r=-.326, P=.001), and bodily pain (r=-.894, P=.001). DISCUSSION: The intensity of chronic pain experienced by the kidney recipients is less than that experienced by patients under chronic hemodialysis, but higher than healthy subjects. Focusing on chronic pain as a cause of post-renal transplantation morbidity is expected to improve post-renal transplantation quality of life.

(32)P colloid radiosynovectomy in treatment of chronic haemophilic synovitis: Iran experience.

Repeated intra-articular bleeding with subsequent development of chronic synovitis and cartilage changes, leading to haemophilic arthropathy, is one the most debilitating problems in haemophilic patients. Radiosynovectomy is a familiar therapeutic choice in management of chronic synovitis in haemophilia. We report the treatments results of synoviorthesis with (32)P chromic phosphate with emphasis on clinical aspects. Between 2002 and 2006 we performed 66 procedures in 53 patients. Seven patients were excluded. The remaining 46 patients were followed for an average of 31 months. The mean age of patients at the time of injection was 15.9 years (range: 6-28). There were three repeat injections. According to Fernandez-pallazi and Cavilgia clinical classification (Table 1) [23], nine joints were Stage II and 46 were Stage III. In latest follow-up, 77% of patients reported at least a 50% decrease in bleeding frequency after treatment (P < 0.0001). The need for antihaemophilic factor consumption dropped by about 74% postradiosynovectomy (P < 0.0001). In most of the injected joints, the range of motion remained stable or improved. A trend was found for the number of haemarthrosis to increase after a period of considerable improvement. Synoviorthesis using (32)P effectively reduces the intra-articular bleeding rate and factor concentrate use. Durability of the response seems to be unpredictable, perhaps attributable to the late intervention. An early radiosynovectomy might be more helpful in terms of stability of response to treatment.

Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disease characterized by prolonged bleeding time with normal platelet count and morphology. It is caused by the quantitative or qualitative deficiency of the platelet glycoprotein IIb-IIIa. In 382 Iranian patients with GT diagnosed at a single center during the period 1969-2001, consanguinity between parents was 86.6%, in accord with the high frequency of intrafamilial marriages in Iran. Almost all patients had had abnormal mucocutaneous bleeding (epistaxis and gum bleeding); at follow-up, 4/5 of the patients had been transfused at least once to control hemorrhagic episodes. As expected, almost all the patients had a normal platelet count while the leukocyte count was increased in 19.3%. Among women, an unexpected low rate of pregnancies was observed.

Carrier testing and prenatal diagnosis of haemophilia B by SSCP in an Iranian family.

Haemophilia B is an X-linked recessive bleeding disorder caused by multiple molecular defects in factor IX gene. During our genotyping programme of haemophilia B patients, a family from the west of Iran was referred to us. We first detected the mutation in the index case of the family by single-strand conformation polymorphism (SSCP) technique. This technique was then applied in carrier detection and prenatal diagnosis for females of this family. Sequencing later revealed the mutation as being G to A at 20519.

Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency.

Prothrombin deficiency is an autosomal recessive disorder associated with a moderately severe bleeding tendency. In this study, 13 patients with prothrombin deficiency were screened for the presence of alterations in the prothrombin gene, and nine novel candidate mutations were identified. Of 11 patients with hypoprothrombinemia, ten are homozygous for five mutations and one patient is a compound heterozygote. The two patients with dysprothrombinemia are homozygous for two mutations. Eight of nine mutations are missense ones associated with single amino acid substitutions in the propeptide (Arg-1Gln, Arg-2Trp), the kringle-1 (Asp118Try) and kringle-2 (Arg220Cys) domains and the catalytic serine protease domain (Gly330Ser, Ser354Arg. Arg382His and Arg538Cys). The ninth mutation is an in-frame deletion of 3 bp that results in the omission of one amino acid (del Lys 301/302). The combination of these missense mutations with crystal structures for alpha-thrombin and the prothrombin fragments 1 and 2 resulted in new insight into the function of alpha-thrombin. The hypoprothrombinemia mutations were inferred to affect either the cleavage of the propeptide from the Gla domain, the stability of the kringle-1 and -2 domains, or the close association of the A and B chains of the serine protease domain. The dysprothrombinemia mutations were inferred to directly affect catalytic function through their location at the active site crevice or exosite 1 within the serine protease domain.

Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von Willebrand disease.

Type 3 is the most severe form of von Willebrand disease (VWD) transmitted as an autosomal recessive trait. We collected data on the clinical manifestations of type 3 VWD by examining 385 patients from 300 Iranian kindreds, who were compared with 100 age-matched patients with severe haemophilia A. Joint and muscle bleeding was less frequent than in haemophiliacs, perhaps because factor VIII levels were in general higher (median value 4% vs. 1% or less). Mucosal tract haemorrhages such as epistaxis and menorrhagia were the most prevalent symptoms in VWD. Post-circumcision and oral cavity bleeding occurred frequently when prophylactic replacement therapy was not carried out or was inadequate. The course of pregnancy was usually uneventful, but increased bleeding occurred at parturition when affected women were treated with replacement therapy for less than 3-4 d. Ten of 385 (2.6%) of these multitransfused patients developed an alloantibody to VWF and 55% are chronically infected with the hepatitis C virus.

Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia.

Knowledge of the spectrum of symptoms in patients with inherited afibrinogenaemia is limited by the rarity of this coagulation defect. We compared a large series of 55 afibrinogenaemic patients from Iran with 100 patients with severe factor VIII deficiency. In afibrinogenaemia there was a higher frequency of mucosal-type bleeding symptoms but joint and muscle bleeding was less frequent and severe than in haemophilia. Umbilical cord bleeding was relatively frequent only in afibrinogenaemic patients. Two young patients developed spontaneous thrombotic episodes and three women had recurrent abortions. Overall, in afibrinogenaemia bleeding symptoms are qualitatively different and less severe than in haemophilia. Afibrinogenaemia can also be accompanied by thrombotic manifestations.

Congenital factor X deficiency: spectrum of bleeding symptoms in 32 Iranian patients.

The spectrum of the clinical manifestations of congenital factor X deficiency was studied in 32 Iranian patients. The most frequent symptom was epistaxis, which occurred in 72% of patients, with all degrees of deficiency. Other mucosal haemorrhages (e.g. haematuria, gastrointestinal bleeding) were less frequent and occurred mainly in patients with unmeasurable factor X. Menorrhagia occurred in half of the women of reproductive age. Soft tissue bleeding occurred in two-thirds of the patients; spontaneous haematomas and haemarthroses led to severe arthropathy in five patients. Bleeding from the umbilical stump was an unexpected finding in nine patients. This study demonstrated that the bleeding tendency of factor X deficiency is severe and correlates with factor levels.

Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII.

Inherited deficiency of factors V and VIII is the most frequent combined coagulation defect. The cases reported so fair are mostly single cases or small series from different centres, making it difficult to evaluate the overall pattern of clinical manifestations of the combined defect. We examined at a single institution 27 Iranian patients. Mucocutaneous and post-surgical bleeding were the most frequent clinical manifestations. The presence of two defects did not make the severity of bleeding greater than that expected in patients with single coagulation defects of similar degrees.

Symptoms of inherited factor V deficiency in 35 Iranian patients.

The type of bleeding symptom has been evaluated in 35 Iranian patients with an inherited deficiency of factor V, with plasma levels between 1% and 10%. The most frequent symptoms included epistaxis and excessive bleeding after surgery. Haemarthroses and muscle haematomas were less common, even in severely deficient patients. More severe symptoms such as gastrointestinal and central nervous system bleeding were rare. The severity of bleeding symptoms was only partially related to the degree of factor V deficiency in plasma. On the whole, human factor V deficiency is characterized by a moderately severe bleeding phenotype.

Alopecia in dolls!

A case of trichotillomania is presented in which symptoms of pulling out a doll's hair preceded by about one year the self-inflicted alopecia in a child.