Parvin Saidi

Age and the prevalence of bleeding disorders in women with menorrhagia.

OBJECTIVE: A study was conducted to evaluate the frequency and types of hemostatic defects occurring in adolescent and perimenopausal-age women diagnosed with menorrhagia. METHODS: A total of 115 women with a physician diagnosis of menorrhagia, including 25 adolescent women, 25 perimenopausal-age women, and 65 women between the ages of 20 and 44, underwent comprehensive hemostatic testing for possible bleeding disorders. Frequencies of bleeding disorders were calculated and compared. RESULTS: Forty-seven percent of women were found to have hemostatic abnormalities, including platelet dysfunction, von Willebrand’s disease, and coagulation factor deficiencies. Adolescents and perimenopausal-age women with menorrhagia were just as likely to have hemostatic abnormalities as were women aged 20 to 44. CONCLUSION: These results demonstrate that underlying bleeding disorders are frequently found in adolescent, postadolescent reproductive age, and perimenopausal-age women presenting with menorrhagia and suggest that women with menorrhagia should be considered for further hemostatic evaluation. LEVEL OF EVIDENCE: II-2

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

Summary.  Menorrhagia is a very common clinical problem among women of reproductive age and recent studies have suggested that underlying bleeding disorders, particularly von Willebrands 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 Willebrands 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.

Management of von Willebrand disease: a survey on current clinical practice from the haemophilia centres of North America.

The optimal treatment of patients with von Willebrand’s disease (vWD) remains to be defined. Moreover, it has not been firmly established which, if any, commonly measured parameters of von Willebrand factor (vWF) protein in the plasma are useful in guiding treatment. To better understand what guidelines physicians follow in the management of vWD, we surveyed 194 North American physicians who are members of the Hemophilia Research Society. Ninety‐nine per cent of responding physicians depend on factor VIII (FVIII):C, vWF:RCo activity and vWF:AG to diagnose vWD, while only 49% use the bleeding time. The minimal goals of treatment for patients undergoing major surgery/trauma or central nervous system haemorrhage were FVIII:C and vWF:RCo activity greater than 80% while levels of more than 50% for minor surgery and dental extractions were considered adequate. Treatment of vWD was based on the type of vWD with type 1 patients being treated most often with desmopressin acetate (DDAVP) alone, types 2A and 2B patients with a combination of DDAVP and a vWF‐containing FVIII product, type 3 patients with vWF‐containing concentrate. Viral infections, including human immunodeficiency virus, hepatitis A, B and C viruses, and parvovirus have been seen in vWD and the efficacy of viral attenuation processes is a major criterion for the selection of treatment by physicians. Based on this survey, prospective studies need to be designed to address the clinical efficacy, safety and predictive value of laboratory monitoring of patients with vWD.

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.

Long term follow-up of arthroscopic synovectomy for chronic hemophilic synovitis

Recurrent hemarthrosis of the knee in hemophiliac patients leads to chronic synovitis, predisposing the joint to further hemarthroses and degeneration. Open synovectomy controls bleeding, however, significant loss of motion frequently results. We are reporting on seven patients who underwent arthroscopic synovectomy and had decreased bleeding episodes while maintaining range of motion. The seven patients had frequent recurrent hemarthroses despite medical management. All had had signs of degenerative arthritis preoperatively. Five of the seven had loss of motion. Length of follow-up averaged 4 years. Six of the seven had reduced bleeding episodes with an average of 0.22 hemarthroses per week. The seventh patient required significantly less Factor to control bleeding. No patient lost more than 10 degrees of motion. Three patients had increases in motion; two were unchanged. Radiographic progression of degenerative changes was noted in five patients, the other two were unchanged. We recommend early arthroscopic synovectomy in the treatment of recurrent hemarthrosis in hemophiliac patients.

Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease.

This study demonstrates that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease randomized to receive niacin, warfarin, antioxidants, or placebo. Changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol (r = 0.61; p < 0.009) in subjects taking niacin.

Methamphetamine intoxication: A speedy new treatment

This communication describes the use of droperidol in methamphetamine poisoning. Droperidol antagonizes the central stimulatory effects of amphetamines producing a person who is indifferent to environmental stimuli, calm and cooperative. Coupled with an acid diuresis, causing a fivefold increase in the urinary concentration of methamphetamine and recovery of 66% of the ingested drug, a seriously intoxicated patient showed rapid improvement.

“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.

Deep Venous Thrombosis Caused by Inferior Vena Cava Atresia and Hereditary Thrombophilia

Inferior vena cava (IVC) atresia is a risk factor for deep vein thrombosis (DVT) in young patients. Although Doppler ultrasound diagnoses DVT, a contrast-enhanced computerized tomography (CT) or magnetic resonance angiography (MRA) diagnoses IVC atresia, other congenital IVC anomalies and must be considered in young patients presenting with idiopathic DVT. Patients with IVC atresia associated with hereditary thrombophilia are at increased risk for recurrent DVT and may require long-term anticoagulation. We report 2 cases: the first one, a 33-year-old man with lower extremity DVT caused by IVC atresia in association with multiple thrombophilic risk factors; the second one, a 34-year-old woman with lower extremity DVT caused by IVC atresia in association with prothrombin gene mutation. To our knowledge, this association has not been reported. The clinical presentation, tools for diagnosis, and the need for long-term anticoagulation are discussed.

Laboratory response to intranasal desmopressin in women with menorrhagia and platelet dysfunction

Summary.  Intranasal desmopressin (IN‐DDAVP) is used for home treatment of menorrhagia in women with inherited bleeding disorders. The effect of IN‐DDAVP on laboratory haemostatic parameters in women with menorrhagia related to platelet dysfunction is unknown. We evaluated the effects of IN‐DDAVP on haemostatic parameters in women with menorrhagia and platelet dysfunction and correlated them with menstrual flow. Eleven women (aged 18–45) with menorrhagia and haemostatic abnormalities had determination of von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo) activity, factor VIII coagulant activity (FVIII:C), platelet aggregation and platelet adenosine tri‐phosphate (ATP) release pre‐IN‐DDAVP and 60‐min post‐IN‐DDAVP. Eight of eleven women underwent platelet function analyzer (PFA‐100) closure time determination with collagen/adrenaline and collagen/adenosine diphosphate cartridges pretreatment and post‐treatment. IN‐DDAVP was administered during two consecutive menstrual cycles. Menstrual flow was assessed during each cycle using a pictorial blood assessment chart. Treatment with IN‐DDAVP resulted in elevated VWF levels and shortened PFA‐100 closure time with significant inverse correlation between shortening of PFA‐100 closure times and increases in VWF levels. There were also significant inverse correlations between changes in menstrual flow and changes in VWF:Ag (P = 0.02), VWF:RCo (P = 0.04) and FVIII:C (P = 0.006), following treatment. In vitro platelet aggregation and platelet ATP release response did not correct and did not correlate with changes in menstrual flow. Our results demonstrate a correlation between haemostatic parameters and menstrual flow following IN‐DDAVP in women with menorrhagia and platelet dysfunction.