PubMed Health⌕ Search

Biomedical subjects

P Saidi

Publications and source records attributed to P Saidi.

At least 19 recordsLinked to original sources

Screening women with menorrhagia for underlying bleeding disorders: the utility of the platelet function analyser and bleeding time.

Menorrhagia is a very common clinical problem among women of reproductive age and recent studies have suggested that underlying bleeding disorders, particularly von Willebrand's deficiency and platelet function defects, are prevalent in women presenting with menorrhagia. The objective of this study was to determine the utility of the platelet function analyser (PFA-100) and bleeding time (BT) as initial screening tests for underlying bleeding disorders in women with menorrhagia. In this study, 81 women with a physician diagnosis of menorrhagia underwent PFA-100 testing, BT and comprehensive haemostatic testing. The effectiveness of the PFA-100 and BT as screening tools in women with menorrhagia was assessed using results of haemostatic testing for von Willebrand's disease (VWD) and platelet dysfunction. In women presenting with menorrhagia, the PFA-100 had a sensitivity 80%, specificity 89%, positive predictive value (PPV) 33%, negative predictive value (NPV) 98% and efficiency 88% for VWD. For platelet aggregation defects, the PFA-100 closure time had a sensitivity 23%, specificity 92%, PPV of 75%, NPV of 52% and efficiency 55%. The data suggest that the PFA-100 may be useful in stratifying women with menorrhagia for further von Willebrand testing; however, neither the PFA-100 nor the BT tests are effective for purposes of classifying women for standard platelet aggregometry testing in women presenting with menorrhagia.

Adolescent↗

Acquired factor VIII inhibitors in non-haemophilic patients: clinical experience of 15 cases.

We retrospectively analysed 15 non-haemophilic patients with acquired factor VIII inhibitors seen in our regional haemophilia centre. The median age was 55 years (range: 21-80). About 70% of patients older than 50 were male, while all five patients younger than 50 were female. The most common underlying condition was pregnancy or postpartum status (20%). About 27% of cases had no identifiable underlying condition. About 27% of patients had medical conditions that were unlikely to be related to acquired inhibitors. The most frequent presenting symptom was spontaneous haemorrhage of soft tissues, skin or joints. Twelve of 13 (92.3%) evaluable patients achieved complete remission (CR) with prednisone alone and/or combined prednisone and cyclophosphamide, but their clinical courses were highly variable. The median time to response was 21.5 weeks (range: 2-176) and the median treatment duration was 9 months (range: 1.25-66). All six patients treated with prednisone initially, and then combined prednisone/cyclophosphamide if no response (NR) to prednisone within 3-4 months (three patients), achieved CR; while four of five patients treated initially with combined prednisone/cyclophosphamide had CR. Patients older than 50 years had a similar response rate, median time to response and median treatment duration as did patients younger than 50 years (83% vs. 100%; 21.5 vs. 32 weeks, and 8 vs 16.5 months, respectively). Furthermore, the differences in the median time to response and treatment duration for patients with high or low baseline or peak inhibitor titres were negligible. Only one patient died of a treatment-related pulmonary aspergillosis 18 months after an acquired inhibitor was diagnosed. None of these patients died of bleeding complications. In conclusion, our patients with acquired FVIII inhibitor had highly variable clinical courses and responses to steroid or immunosuppressive therapy. The inhibitors in the majority of patients resolved in less than 6 months although in two cases it persisted for longer than 1 year before resolving. Treatment with prednisone alone as first line, then combined prednisone with cyclophosphamide if NR to prednisone seemed equally effective when compared with using combined prednisone and cyclophosphamide initially. Further studies of newer therapeutic agents such as 2-chlorodeoxyadenosine (2-CDA) and rituximab are warranted for patients refractory to conventional immunosupressive therapy.

Adult↗

Platelet functional defects in women with unexplained menorrhagia.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17-55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia.

Adolescent↗

Deletion polymorphism in the angiotensin-converting enzyme gene as a thrombophilic risk factor after hip arthroplasty.

Despite thromboprophylaxis, deep vein thrombosis is a common complication of major orthopedic surgery. Predisposing genetic risk factors are unknown. In this case-control study, we investigated the association of the insertion (I)/deletion (D) angiotensin converting enzyme (ACE) gene polymorphism, Factor V Leiden (R506Q) mutation, and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with post-operative venous thrombosis in 85 patients who underwent elective total hip arthroplasty. The odds of a thrombotic event following hip surgery among subjects with the DD genotype of the ACE gene was increased more than 10-fold compared to subjects with the II genotype (odds ratio 11.7 [95% confidence interval 2.3-84.5]); it was increased 5-fold in subjects with the ID genotype compared to the II genotype (odds ratio 5.0 [95% confidence interval 1.1-34.9]). Mean plasma ACE level in control subjects not on ACE inhibitors at the time of study (n=43) was lowest in persons homozygous for the I allele (18.9+/-7.95 U/l), intermediate in patients with the ID genotype (31.6+/-10.8 U/l) and highest in subjects homozygous for the D allele (44.0+/-7.14 U/l). Mean plasma ACE level among cases was higher (33.0 U/l, n=25) than among controls (29.4 U/l, n=43) but this difference was not statistically significant. Neither the Factor V Leiden mutation nor MTHFR gene polymorphism increased the risk of thrombosis following hip replacement. These results demonstrate that the I/D ACE gene polymorphism is a potent risk factor for thrombosis in subjects undergoing total hip arthroplasty.

Activated Protein C Resistance↗

Plasma tissue factor antigen levels in capillary whole blood and venous blood: effect of tissue factor on prothrombin time.

To measure the amount of tissue factor released during specimen collection and its potential effect of shortening the prothrombin time, we measured tissue factor and prothrombin time in twenty-three paired venous and capillary blood samples from anticoagulated patients and in ten paired samples from controls. We also compared venous prothrombin time determined by a plasma-based assay with venous and capillary prothrombin time determined with a whole blood assay. Venous specimens were obtained using a two-syringe technique; capillary specimens were obtained by fingerstick after wiping the first drop of blood. Plasma tissue factor was determined by an enzyme-linked immunoabsorbant assay. The patients' mean venous tissue factor (235 +/- 101 pg/ml) and capillary tissue factor (268 +/- 106 pg/ml) were higher than those of the controls (161 +/- 42 pg/ml and 187 +/- 63 pg/ml, respectively, P < 0.05). These differences disappeared after adjusting for age. Capillary tissue factor levels were higher than venous tissue factor (244 +/- 102 pg/ml vs. 213 +/- 93 pg/ml), with a mean difference of 31 pg/ml (P = 0.0001). In addition, whole blood prothrombin time was lower in the capillary than in the venous samples (17.7 +/- 5 sec vs. 18.3 +/- 5.4 sec, P = 0.004). However, there was no correlation between capillary-venous differences in tissue factor and capillary-venous differences in the whole blood prothrombin time. Whole blood capillary and venous prothrombin times highly correlated with the plasma-based venous prothrombin time (r = 0.98, P < 0.0001). These results demonstrate that obtaining blood by fingerstick does not result in a clinically significant release of tissue factor. In addition, we did not observe any interference of plasma tissue factor with the whole blood prothrombin time assay. A direct relationship between tissue factor and age was observed.

Adult↗

Association of hemostatic factors with peripheral vascular disease.

Hemostatic risk factors have been well established in coronary artery disease but less well studied in peripheral vascular disease. The relationship of coagulation and fibrinolytic proteins to lower limb arterial occlusive disease and other vascular risk factors remains poorly defined. Fibrinogen, factor VII coagulant activity, von Willebrand factor (vWf) antigen, and plasminogen activator inhibitor-1 (PAI-1) activity were measured in 46 adult participants in the Arterial Disease Multiple Intervention Trial (ADMIT) and in 76 control subjects and related to ankle-brachial systolic pressure index (ABI), a measure of lower limb arterial stenosis. The primary inclusion criterion for the ADMIT study population was an average of two ABIs <0.85. Fibrinogen and PAI-1 in ADMIT subjects were significantly higher than in control subjects (331 +/- 52 mg/dl vs 273 +/- 46 mg/dl, p < 0.0001; 18.7 +/- 10 units/ml vs 13.5 +/- 8.9 units/ml, p < 0.04). There were significant correlations of fibrinogen with ABI, factor VII coagulant activity, and systolic and diastolic blood pressures; PAI-1 with body mass index and age; and factor VII coagulant activity with cholesterol levels. Logistic regression analysis, considering hemostatic variables and several known nonhemostatic risk factors of peripheral arterial disease, showed that fibrinogen and systolic blood pressure were independently associated with ABI status in this population. The results demonstrate a strong independent correlation between fibrinogen levels and the presence of lower limb arterial stenosis. PAI-1 levels were elevated in ADMIT participants, but multivariate analysis did not demonstrate an independent relationship between PAI-1 and ABI.

Aged↗

Concurrent presentation of erythrocytic and megakaryocytic aplasia.

A case of a patient presenting with idiopathic concurrent erythrocytic and megakaryocytic aplasia is reported. The patient's response to immunosuppressive therapy and her bone marrow pathology clearly suggest an immune mechanism. Based on the lack of suppression of erythroid colony growth, several mechanisms are postulated. Well-established molecular and genetic evidence, along with clinical observations, suggests that a relationship exists between the erythrocytic and megakaryocytic cell lines. This may be related to a common bipotential stem cell or common cell surface markers. This case provides strong clinical evidence to support this relationship.

Adult↗

Primary extramedullary leukemia of the prostate: case report and review of the literature.

We present the case of a 67-year-old male with primary extramedullary leukemia of the prostate gland, the first reported case in the literature to the best of our knowledge. His initial symptoms consisted of episodes of urinary retention. He underwent transurethral resection of the prostate, and a diagnosis of high-grade lymphoma was rendered. He then received a course of doxorubicin-based lymphoma chemotherapy regimen. However, based on a panel of immunocytochemical stains, a diagnosis of extramedullary leukemia or chloroma was confirmed. His bone-marrow examination at this point was normal. He underwent radiation therapy to the prostate with a total dose of 3960 cGy. Seven months after his initial presentation, he progressed to acute nonlymphocytic leukemia (ANLL), M2 by FAB classification. He was successfully treated with induction and consolidation chemotherapy with Ara-C and idarubicin, and was maintained in complete remission up to 19 months of follow-up. Eight other cases of prostatic leukemia reported in the literature are presented. Five cases occurred in association with ANLL, 2 cases as sites of ANLL relapse, and 1 case in association with myelodysplasia. The use of immunohistochemical stains has aided us in diagnosis of extramedullary leukemia. Surgery, radiation therapy, and chemotherapy play complementary roles in the treatment of prostatic extramedullary leukemia.

Aged↗

Acute promyelocytic leukemia in pregnancy: all-trans retinoic acid as a newer therapeutic option.

BACKGROUND: Acute promyelocytic leukemia is a unique subset of acute myelogenous leukemia, characterized by a neoplastic proliferation of promyelocytes and a prompt response to all-trans retinoic acid (tretinoin), which induces differentiation of immature leukemic promyelocytes into mature neutrophils. Because of the high incidence of disseminated intravascular coagulation (DIC) associated with acute promyelocytic leukemia and the danger of exacerbation of DIC with pregnancy, management of acute promyelocytic leukemia during pregnancy requires prompt and careful attention. CASE: A 29-year-old woman in her third trimester was diagnosed with acute promyelocytic leukemia and DIC. The infant was delivered by cesarean and the mother was successfully treated with tretinoin, inducing the leukemic promyelocytes to differentiate into mature granulocytes and possibly reversing the DIC. CONCLUSION: If the fetus can be delivered safely, tretinoin as a single agent is an option for the initial treatment of maternal acute promyelocytic leukemia because it does not suppress the bone marrow and may ameliorate DIC. Because of the danger of hyperleukocytosis, chemotherapy should be added initially if the white blood cell count is greater than 5000/microL. If the fetus cannot be delivered at a viable stage, conventional cytotoxic chemotherapy is the alternative option.

Adult↗

Purified factor IX using monoclonal immunoaffinity technique: clinical trials in hemophilia B and comparison to prothrombin complex concentrates.

Replacement therapy for hemophilia B (factor IX deficiency) using prothrombin complex concentrate (PCC) has been associated with serious complications of thromboembolic events and transmission of viral infections. Monoclonal antibody-purified factor IX (Mononine) provides a highly purified factor IX concentrate, while eliminating other vitamin K-dependent factors (II, VII, and X). Mononine was evaluated for in vivo recovery, half-life, and for its safety and efficacy in 10 patients with hemophilia B. The in vivo recovery of factor IX with Mononine was a 0.67 +/- 0.14 U/dL (mean +/- SD) increase per 1U/kg of infused factor IX, and the biologic half-life (t1/2), determined using the terminal phase of elimination, was 22.6 +/- 8.1 hours. Comparison of in vivo recovery of other vitamin K-dependent factors following a single infusion of either Mononine or PCC showed that, whereas Mononine infusion caused no changes in other vitamin K-dependent factors or in prothrombin activation fragment (F1+2), PCC infusion was associated with significant increases of factors II (2.7 U/dL per 1 U/dL of IX increase) and X (2.2 U/dL for 1 U/dL for 1 U/dL of IX). Patients who used Mononine as their sole therapeutic material during the 12-month period showed an excellent response in hemostasis for their bleeding episodes. Their experience with long-term use of Mononine was at least equivalent to their previous experience with PCC in the frequency and amount of factor usage. No patients developed antibody against mouse IgG or an increase in IX inhibitor during the 12-month period. These results indicate that monoclonal antibody-purified factor IX concentrate provides hemostatically effective factor IX replacement while avoiding extraneous thrombogenic substances.

Antibodies, Monoclonal↗

"Superwarfarin" ingestion. A new problem in covert anticoagulant overdose.

For the attention of psychiatric consultants, brodifacoum, a new longer-acting, warfarin-like oral anticoagulant rodenticide, has been used for suicide attempts. The overdose potential with brodifacoum is serious since it is readily available without prescription, and bleeding complications last for weeks to months after a single ingestion. This article reports a case of ingestion and reviews four similar cases from medical literature. Also reviewed are details about mechanism of action, procedures for diagnosis, and treatment requirements. Also, characteristics of persons who ingest long-acting anticoagulants appear to differ from those who ingest short-acting anticoagulants reported from earlier literature.

4-Hydroxycoumarins↗

Clinical experience of a new monoclonal antibody purified factor IX: half-life, recovery, and safety in patients with hemophilia B.

Highly purified factor IX, produced by a monoclonal antibody immunoaffinity technique, contains a high concentration of factor IX with negligible amounts of other vitamin K-dependent coagulation factors. When infused in patients with hemophilia B, monoclonal factor IX concentrate yielded a mean half-life of 34.6 +/- 13.1 (+/- SD) hours and in vivo recovery of 0.67 +/- 0.14 U/dL rise per each U/kg of factor IX infused. Unlike prothrombin complex concentrate (PCC) infusion, monoclonal IX infusion was not associated with rises in factors II, VII, and X, but achieved in vivo recovery and half-life at least comparable to PCC. Long-term use of monoclonal IX as a home-care product provided excellent response in the control of bleeding episodes and was equivalent to previous patient experience with PCC. The results indicate that monoclonal IX concentrate raises factor IX levels effectively, while avoiding extraneous thrombogenic components.

Adult↗

Human immunodeficiency virus (HIV) infection in haemophiliacs: long-term prognostic significance of the HIV serologic pattern.

To identify markers of prognostic value in the course of HIV disease, immunologic parameters and profiles of HIV antibodies and antigen were studied in 60 haemophiliacs. The 43 HIV-seropositive subjects were followed prospectively over a 4 year period with a retrospective analysis as well of their frozen plasma for HIV markers. This group had a significant decrease in number of helper/inducer T lymphocytes as compared with 17 HIV seronegative subjects. The degree of changes correlated with the stage of disease, with the most severe depletion of CD4 cells in those who developed AIDS. Counts of B cells and platelets were also lower in HIV-infected haemophiliacs. Ten out of 12 AIDS patients had undetectable antibodies to HIV p24 antigen; low levels of p24 antibody were also seen in six out of 15 subjects with lymphadenopathy (CDC stage III), but in only two out of 16 asymptomatic subjects (CDC stage II). Sustained HIV p24 antigenaemia (greater than 30 pg/ml) was seen in 10 AIDS patients, in five subjects with lymphadenopathy and in two asymptomatic haemophiliacs. Initial HIV serologic profiles, obtained when all patients were asymptomatic, were highly predictive for progression of the HIV infection: the initial pattern of low anti-p24 antibody and positive p24 antigenaemia conferred the worst prognosis, with all patients in this group developing ARC or AIDS within 36 months, whereas an initial high level of anti-p24 without p24 antigenaemia was associated with relatively the best prognosis. Of such subjects, 58% have remained clinically asymptomatic after 48 months of the study (P less than 0.00001). The serologic profile of HIV antibody pattern and HIV antigen in haemophilic patients thus already provides important prognostic information at an early stage of HIV infection.

AIDS Serodiagnosis↗