Acquired von Willebrand syndrome in multiple myeloma

Acquired von Willebrand syndrome (AvWS) is an uncommon complication of multiple myeloma (MM), and it is believed to be connected with paraprotein. The aim of this study was to determine the incidence of AvWS in patients with MM, and estimate the role of paraprotein in its occurrence. The study included 40 patients with MM. The plasma level of paraprotein, platelet adhesion on glass pearls, plasma von Willebrand factor antigen concentration, and ristocetin-induced platelet aggregation (RIPA) were measured initially. Absence of RIPA was found in six patients with MM (15%); however, all six of them had normal levels of von Willebrand factor antigen. Paraprotein was isolated from the serum of these patients. Platelet aggregation was measured in six healthy donors before and after addition of the isolated paraprotein. RIPA was significantly decreased in healthy donors in the presence of paraprotein (P lt 0.001). The same test was repeated with added human immunoglobulins for intravenous use without any change in RIPA. A significant negative correlation between plasma paraprotein level and RIPA was found (P lt 0.001). These investigations have shown that paraprotein is associated with AvWS in patients with MM

Clinical significance of optimal red cell mass and plasma volume estimation methods

BACKGROUND: The aim of this study was to present and compare the results of proposed methods for optimal red cell mass and plasma volume (RCM&PV) estimation, and their influence on the interpretation of obtained results. MATERIAL AND METHODS: In 120/280 patients with polycythaemia rubra vera, subjected to RCM&PV determination with autologous erythrocytes in vitro labelled with 51Cr-sodium chromate, optimal volumes were determined using: 1. traditional ml/kg of: - the real body weight method (ml/kg RBW); - the optimal body weight method (ml/kg OBW). 2. the body weight, height, and sex based method (Retzlaff's tables), 3. the method recommended by the International Council for Standardization in Haematology (ICSH), based on body surface area. RESULTS: Different interpretation of the same results of 120 RCM&PV measurements was registered in 48/120 patients (40%). The greatest disagreement existed between ml/kg RBW and ml/kg OBW methods (in 39/120 subjects, 32.5%). In underweight patients the ml/kg RBW method, and in overweight patients the ml/kg OBW method, offered better agreement with ICSH&Retzlaff's methods. The ml/kg RBW method disagreed with ICSH&Retzlaff's methods and ml/kg OBW in 25% and 19.2% of patients respectively. ICSH and Retzlaff's methods disagreed in 10/120 patients (8.3%). The ICSH method yielded significantly lower optimal volumes than Retzlaff's. CONCLUSION: Three methods for optimal RCM&PV estimation lead to different interpretations of the same results of RCM&PV measurements with 51Cr-erythrocytes in 40% of patients. Two ml/kg body weight methods show greater disagreement in comparison with ICSH and Retzlaff's methods, which differ significantly. The ICSH method yields lower optimal values compared to Retzlaff's

Successful non-standard approaches to massive hemoptysis in invasive pulmonary aspergillosis

Introduction. Invasive pulmonary aspergillosis (IA) is the most frequent invasive fungal infection in patients with hematological malignancies. Massive hemoptysis (MH) with blood loss more than 300- 600 ml in 24 hours is a rare (5-10% of IA patients) but frequently fatal complication. Standard treatment of MH, such as oxygenation, a semi-sitting position with the bleeding site down, bronchoscopical suctioning, antifungal therapy, transfusion support and surgical resection might be either ineffective or not feasible in some cases. Outline of Cases. We report two patients with life threatening, non-controlled, massive hemoptysis who were successfully managed by non-standard measures. A 61-year-old male with acute myeloid leukemia developed pulmonary IA and massive hemoptysis after consolidation cure by chemotherapy. The bleeding site was localized in the VI lung segment by bronchoscopy. Local application of fibrinogen-thrombin concentrate (fibrin glue) stopped the bleeding. A 22-year-old female patient with the diagnosis of severe aplastic anemia developed IA and massive hemoptysis early after application of immunosuppressive therapy (antilymphocyte globulin, cyclosporine and corticosteroids). Conventional transfusion therapy, desmopresine and antifibrinolytics were ineffective. This urgent condition was successfully treated with human activated recombinant factor VII (rFVIIa, NovoSeven®). Conclusion. Our experience together with data from the available literature suggests a potential benefit of fibrinogen-thrombin concentrate and rFVIIa in the treatment of refractory critical bleeding in hematooncological patients

Primary systemic amyloidosis

Background. Systemic amyloidosis is a rare disorder which usually occurs in aged persons and has a poor prognosis. Systemic amyloidosis can be primary, occasionally associated with multiple myeloma, or secondary, associated with another disease. Case report. We presented a 72-year-old male patient with periocular purpura ("racoon sign") and waxy papules, petechiae and ecchymoses on the neck and thoracic area. Purpuric macules were present also on the lips and tongue which was edematous (macroglossia). The skin lesions occurred two years earlier, the patient lost more than 15 kilograms of the body mass for less than a year. Immunoelectrophoresis of urine and serum demonstrated the presence of immunoglobulin light chains of the circulating monoclonal protein. Histopathological examination of skin lesions showed Congo red positive deposits in the derm. Cardiac evaluation revealed the signs of heart failure, and renal evaluation revealed nephrotic syndrome, with excessive protein lost. He was treated with oral melphalan and prednisolone, and died 7 days after starting the therapy due to heart failure. Conclusion. This patient considered as a rare case with systemic amyloidosis highlights the importance of histopathological and physical examination in any cases with periocular purpura, petechiae, ecchymoses and macroglossia

Protein S and pregnancy: Report of a case

Protein S is a cofactor of protein S which lowers the activat- ed factors VIII and V. Pregnancy reduces the level of protein S to 40-50% of normal levels but it is not clear whether the lowered protein S levels increase the risk of developing thrombo-embolism during pregnancy. This is a report of a 39-year old woman, multipart whose pregnancy terminated as IUGR and who had previously two stillbirths. After the third pregnancy loss of functional protein S level was 20%. Two months after delivery protein S activity was 60%. As it was suspected that low protein S level was a risk factor of complications in pregnancy anticoagulant therapy was used. Thereafter pregnancy and delivery at 38.5 weeks of gestation were successful and the baby weighted 3400 gr at birth. The aim of this report is to emphasize the important role of follow-up of the level of protein S in pregnancy in order to avoid the risk of thrombo-embolism in pregnancy. Anticoagulant therapy is very successful in such a pregnancy and may ensure safe birth

Mesenteric and splenic venous thrombosis in a female patient with essential thrombocytosis and the resistance to activated protein C

Splenic venous thrombosis is a rare disease in which an underlying hypercoagulable state can often be found. A 27-years old female patient with recurrent mesenteric venous and splenic thrombosis as a severe complication of an association of resistance to activated protein C and essential thrombocythemia is presented in this report. Establishing the diagnosis of essential thrombocytosis was particularly difficult because this was the case of the so called "silent" myeloproliferative disorder. The number of thrombocytes was almost normal before the splenectomy performed because of the splenic venous thrombosis. Thus, spontaneous growth of erythroid and megakaryocyte colonies in vitro and the clinical course of the disease were the clues for establishing the diagnosis, because the number of thrombocytes reached the values over 1500×109/l after only 1.5 years of the follow-up. The case of this patient was interesting particularly from the surgical point of view because of the management strategy

Preoperative blood transfusion for gynecological operation of a patient with Bernard-Soulier syndrome: Case report

Bernard-Soulier syndrome belongs to congenital thrombocytopathic platelet disorders. There is a change of the structure of the glycoprotein in platelet membrane, causing the impair of platelet adherence on the blood vessel wall. This syndrome is clinically manifested by spontaneous bleeding in the skin and mucosa. The prognosis is usually good with an adequate support, but serious bleeding episodes occur during menstruation, trauma or surgery intervention. Treatment of bleeding or prophylaxis during surgical intervention is usually based upon platelet transfusion and the use of antifibrinolitic drugs. The object of case report is the significance of the right and an adequate preparation for the operational treatment: Mrs 42 year old, with diagnosis: Bernard-Soulier thrombocytopathia. Iron deficiency anemia. Status post operationem cystis ovarii sinistri. Admitted to the Clinic of gynaecology and obstetrics 'Narodni front' for operative treatment. The menstrual cycle is on 28 days, duration 7 days. From juvenile period there were reports of episodes of bleeding with thrombocytopathia. In prepartal period transfused with few doses of platelet. All dental interventions followed with bleeding, done with 6 doses of platelet concentrate. The history of operation of a cyst with a diagnosis: Cysta ovarii lateralis dextri torquata in 2005. The operation followed with pre-operative use of 15 doses of platelet concentrate, 2 units of fresh frosen plasm and 3 units of deplasmatic erythrocytes. There was a report of adverse reaction due to plasm transfusion and erythrocytes as a hypersensitive reaction, but during operation, there was no bigger post-operative bleeding. In following 2 years, the patient was hospitalized few times because of seriuos menometrorrhagia, and conservativly treated with iron preparations, with a difficult tolerating. Anamnesis: allergy to preparation of salicylate, ranitidin, diclofenac and tranexamic acid. In last hospitalization, the patient was admitted because of a large bleeding. Haematological parameters: Hgb 63 g/L, Rbc 2,61 x 1012/l, MCV 76fL, Plt 22 x 109/l. Biochemical parameters in referential values. Global tests of haemostasis preoperativly: PT 13,4s (9-12,6s), INR 1,02, APTT 20,7s (24-35s), fib 2,08 g/L (1,69-5,15 g/L), TT 18,9s (18-25s), 3 doses of deplasmatic erythrocytes and 2 x 7 doses of platelet concentrate with preoperativly used of methylprednisone (80 mg). Operation: Hysterectomia totalis abdominalis classica cum adnexectomiam lateralis dextri. Pre-operative and post-operative period regular. Therapy: antibiotics, analgetics, infusion solutions and 5 x 7 doses of platelet concentrate with methylprednisone (80 mg). Wound healing per primam. The patient was discharged from the Clinic well recovered, with a plan for a treatment and a future care needs

FV Leiden mutation and risk of recurrent venous thromboembolism in Serbian population

The absolute rate of recurrence of venous thromboembolism (VTE) is approximately 5% per year. There is a lower rate of recurrence in provoked VTE, and higher in idiopathic one. So far, there is no consensus whether hereditary thrombophilia should be considered as a persistent risk factor, and whether it requires long-term anticoagulant therapy. The aim of our study was to estimate the risk of recurrent VTE in patients carrying FV Leiden mutation in Serbian population. In retrospective study (1994-2006), we have evaluated the risk of recurrent VTE in 56 patients who are carriers of FV Leiden mutation, in comparison to group consisting of 56 patients non-carriers of FV Leiden mutation. Patients with FII G20210A and MTHFR C677T mutations, antiphospholipid antibodies, antithrombin III, protein C or protein S deficiency, malignancies and diabetes were excluded from the study. Recurrent VTE occurred in 44.6% of the patients, carriers of the FV Leiden mutations, vs. 26.7% in non-carriers group (P lt 0.05). The incidence rate was 3.7 and 2.2% per year, respectively. The estimated relative risk of recurrence for FV Leiden carriers was 1.67 (95% CI 0.99-2.81, P = 0.049). The 60% of patients with mutation and only 13% without mutation develop rethrombosis during first year after discontinuance of therapy (P lt 0.01). In our study patients with symptomatic VTE who are carriers of the FV Leiden gene mutations have a higher risk of recurrent VTE than non-carriers. Our data suggest the importance of the FV Leiden mutation detection and the estimation of the clinical condition for successful secondary prophylaxis of VTE

The use of D-dimer with new cutoff can be useful in diagnosis of venous thromboembolism in pregnancy

Objective: D-dimer testing has an important role in the exclusion of acute venous thromboembolism (VTE) in the nonpregnant population. Establishing D-dimers role in the diagnosis of VTE in pregnancy is hampered because of the substantial increase of D-dimer throughout gestational age. Study design: In a prospective study we followed 89 healthy pregnant women to establish the reference range of D-dimer for each trimester. D-dimer testing was also performed in 12 women with clinical suspicion of VTE and their results were compared with the established new reference range of D-dimer, and with the recorded ultrasound findings. Results: In the first trimester, 84% women from reference group had normal D-dimer, in the second 33%, and by the third trimester only 1%, which suggests that D-dimer has no practical diagnostic use in ruling out VTE if the threshold of 230 ng/mL for abnormal is used. All pregnant women with thrombosis who had positive ultrasound findings also had statistically significant elevation of the D-dimer level, considering the established reference range of the corresponding trimester. We found 100% sensitivity of D-dimer test. A women developed thrombosis in the first trimester had 6.7-7.6 time higher level of D-dimer than the mean value in the reference group, and in the third trimester thrombotic women had 2.0-3.8 time higher level of D-dimer, p lt 0.0001. Conclusion: D-dimer test with the new threshold for: the first of 286, the second of 457 and the third trimester of 644 ng/mL can be useful in diagnosis of pregnancy related VTE