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ABSTRACT: Bleeding with severe aortic stenosis is linked to acquired von Willebrand syndrome and loss of high-molecular-weight multimers of von Willebrand factor. Valve replacement resolves bleeding tendency and loss of high-molecular-weight multimers. We report outcomes in 5 patients with symptomatic obstructive hypertrophic cardiomyopathy and spontaneous gastrointestinal, mucosal, or excessive postsurgical bleeding in whom acquired von Willebrand syndrome was documented. All 5 patients underwent surgical septal myectomy with resolution of acquired von Willebrand syndrome.
Mayo Clinic Proceedings 03/2011; 86(3):219-24. · 5.70 Impact Factor
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ABSTRACT: Electrophoretic analysis of plasma von Willebrand factor (VWF) multimer distribution and infrastructure is essential for subtyping von Willebrand disease. To improve the sensitivity, precision and efficiency of this assay, we developed and validated a new in-gel infrared fluorescent VWF multimer imaging method to visualize and quantify VWF multimers directly in the agarose gel, thus eliminating electroblotting or autoradiographic steps.
VWF multimer analyses of plasma samples from 34 patients with known von Willebrand disease or acquired von Willebrand syndrome, 9 patients with acquired VWF abnormalities, 26 normal volunteer donors and 49 patient samples referred for von Willebrand factor multimer analysis were performed by both traditional autoradiographic and the new infra-red imaging methods and compared. VWF multimer image data were electronically acquired, archived and analyzed.
The in-gel infrared method has a sensitivity of detecting VWF antigen as low as approximately 1.6 IU/dL, a reliable fluorescent intensity with intra- and inter-day variability (CV) of 5% and 6% respectively, and provides superior imaging resolution and shortened test turnaround time. Using intermediate resolution agarose gel electrophoresis, the infra-red method sensitively detects subtle loss of highest molecular weight von Willebrand factor multimers in plasmas with acquired VWF abnormalities and in commercial normal reference plasmas, and provides evidence of increased proteolysis of ultralarge multimers in some type 2 VWD plasmas.
The in-gel infrared fluorescent VWF multimer imaging method provides a sensitive, reliable, efficient and robust system to improve laboratory testing for von Willebrand disease classification.
Thrombosis Research 10/2010; 126(6):543-9. · 2.44 Impact Factor
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ABSTRACT: Von Willebrand disease is an inherited condition characterized by deficiency of von Willebrand factor, which is essential in hemostasis. The National Heart, Lung, and Blood Institute has released new evidence-based guidelines for the diagnosis and management of the disease. There are three major subtypes of von Willebrand disease, classified as partial quantitative deficiency (low levels) of von Willebrand factor (type 1), qualitative deficiency (type 2), or virtually complete deficiency (type 3). Diagnosis is usually made by reviewing the patient's personal and family history of bleeding and by clinical evaluation for more common reasons for bleeding, supplemented with laboratory tests. Assessment may be used to determine bleeding risk before surgery and other invasive procedures, and to diagnose reasons for unexplained hemorrhaging. Von Willebrand factor levels of 30 IU per dL or lower are required for the definite diagnosis of inherited von Willebrand disease. Persons with levels of 30 to 50 IU per dL may not have the disease, but may need agents to increase von Willebrand factor levels during invasive procedures or childbirth. Treatment is tailored to the subtype of the disease: increasing plasma concentration of von Willebrand factor by releasing endogenous stores with desmopressin or replacing nonexistent or ineffective von Willebrand factor by using human plasma-derived, viral-inactivated concentrates; treatment is often combined with hemostatic agents that have mechanisms other than increasing von Willebrand factor. Regular prophylaxis is seldom required, and treatment is initiated before planned invasive procedures or in response to bleeding.
American family physician 12/2009; 80(11):1261-8. · 1.70 Impact Factor
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ABSTRACT: Von Willebrand disease (VWD) is the most common inherited bleeding disorder and may affect as many as one in 100 women. The condition results from a deficiency, dysfunction, or absence of von Willebrand factor (VWF). In women, the most common symptom of VWD is menorrhagia. Of women with menorrhagia, 5-20% have been found to have previously undiagnosed VWD. Besides menorrhagia, women with VWD are more likely to experience other conditions that manifest with abnormal reproductive tract bleeding. The patient with a suspected bleeding disorder should be referred to a hemophilia treatment center or hematologist with expertise in bleeding disorders for definitive diagnosis. After diagnosis, the first choice of therapy for the management of menorrhagia in adolescents or adult females who do not desire child bearing is still hormonal contraceptives. Women who fail hormonal contraceptives, yet desire future child bearing, and women who desire pregnancy are candidates for hemostatic therapy, which is generally reserved for patients with VWF levels less than 50 international units/dL. During pregnancy, VWF levels rise, frequently obviating the need for hemostatic therapy at the time of delivery. Minor procedures can be managed with 1-desamino-8-D-arginine vasopressin, antifibrinolytic medication, or both, but major surgery or childbirth requires replacement with VWF and should be conducted in a center with available hematologists, anesthesiologists, pharmacists, and laboratory support experienced in the management of bleeding disorders. LEVEL OF EVIDENCE: III.
Obstetrics and Gynecology 10/2009; 114(3):674-8. · 4.73 Impact Factor
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ABSTRACT: Although typically a disorder of adults, acquired von Willebrand syndrome (AVWS) is increasingly being recognized in the pediatric population in association with congenital cardiac diseases, certain neoplasia, and hypothyroidism. Transplacental transfer of maternal immunoglobulin G (IgG) antibodies as a cause of neonatal disorders in infants born to mothers with autoimmune conditions has been reported. We describe the diagnosis and peripartum clinical management of AVWS due to monoclonal gammopathy of undetermined significance (MGUS) and the first reported case of transient neonatal AVWS due to transplacental transfer of maternal IgG antibodies.
Pediatric Blood & Cancer 06/2009; 53(4):655-7. · 1.89 Impact Factor
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ABSTRACT: Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd).
American Journal of Hematology 04/2009; 84(6):366-70. · 4.67 Impact Factor
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ABSTRACT: Laboratory tests for lupus anticoagulants (LA) are commonly performed to evaluate thrombosis or suspected phospholipid antibody syndromes. To determine current LA testing practices, and if they conform to published recommendations, two questionnaires were distributed to clinical laboratory members of the North American Specialized Coagulation Laboratory Association (NASCOLA) and the ECAT Foundation (ECAT). The first and second questionnaires were completed by 113 and 96 laboratories, respectively. Commonly performed LA tests included the dilute Russell's viper venom time, LA sensitive activated partial thromboplastin time and hexagonal phospholipid test. Although some laboratories did single LA tests if requested, the majority complied with published recommendations: to use platelet poor plasma for LA tests; to use two or more screening tests, representing different assay principles, and one assay having a low phospholipid concentration to exclude LA; to confirm LA phospholipid dependency by the method giving an abnormal LA screen; to document the inhibitor activity on pooled normal plasma; and not to use phospholipid antibodies to confirm LA. A minority (<35%) followed the recommendations to exclude factor deficiencies and factor inhibitors as the cause of an abnormal LA test. After participating, 32% of laboratories had changed practices and 20% indicated that they would be changing practices. While most laboratories generally follow published guidelines for LA testing, few follow recommendations to evaluate for other coagulation abnormalities. Questionnaires may be helpful quality initiatives to improve compliance with laboratory testing guidelines and recommendations.
Thrombosis and Haemostasis 02/2009; 101(1):178-84. · 5.04 Impact Factor
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ABSTRACT: For patients with plasma coagulation factor XIII (pFXIII) deficiency, recommended means of replacement include infusions of fresh-frozen plasma (FFP), cryoprecipitate, or (where available) factor (F)XIII concentrates. Quantitative differences in pFXIII concentration in FFP and cryoprecipitate are not well defined and were, therefore, the subject of this study.
FFP and cryoprecipitate (10 bags each from blood group O donors) were analyzed to quantify pFXIII activity and antigen. Coagulation FVIII, fibrinogen, and von Willebrand factor (VWF) were also quantitated.
Mean (+/-SD) pFXIII activity in cryoprecipitate and FFP bags was 60 +/- 30 and 288 +/- 77 U per bag, respectively, and pFXIII antigen and activity levels were concordant. Other comparisons (mean +/- SD) between cryoprecipitate and FFP, respectively, were as follows: coagulation FVIII activity, 133 +/- 37 and 265 +/- 83 U per bag; fibrinogen content (Clauss kinetic assay), 183 +/- 44 and 725 +/- 199 mg per bag; VWF antigen content, 181 +/- 53 and 218 +/- 70 U per bag; VWF ristocetin cofactor activity, 168 +/- 34 and 221 +/- 65 U per bag; VWF collagen-binding activity, 164 +/- 40 and 208 +/- 71 U per bag; and fluid (plasma) volumes per bag, 21.3 +/- 2.7 and 245 +/- 29 mL.
In contrast to other cryoprecipitable coagulation proteins, pFXIII is only mildly enriched in cryoprecipitate when compared with FFP (approx. two- to threefold). Although both products can provide effective pFXIII replacement, FFP may be preferred when infusion volume is not a major consideration and pFXIII concentrates are not available. VWF is substantially enriched in cryoprecipitate (approx. ninefold compared with its concentration in FFP), with VWF activity content exceeding that of FVIII by approximately 26 percent on average.
Transfusion 01/2009; 49(4):765-70. · 3.22 Impact Factor
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ABSTRACT: BACKGROUND: For patients with plasma coagulation factor XIII (pFXIII) deficiency, recommended means of replacement include infusions of fresh-frozen plasma (FFP), cryoprecipitate, or (where available) factor (F)XIII concentrates. Quantitative differences in pFXIII concentration in FFP and cryoprecipitate are not well defined and were, therefore, the subject of this study.STUDY DESIGN AND METHODS: FFP and cryoprecipitate (10 bags each from blood group O donors) were analyzed to quantify pFXIII activity and antigen. Coagulation FVIII, fibrinogen, and von Willebrand factor (VWF) were also quantitated.RESULTS: Mean (±SD) pFXIII activity in cryoprecipitate and FFP bags was 60 ± 30 and 288 ± 77 U per bag, respectively, and pFXIII antigen and activity levels were concordant. Other comparisons (mean ± SD) between cryoprecipitate and FFP, respectively, were as follows: coagulation FVIII activity, 133 ± 37 and 265 ± 83 U per bag; fibrinogen content (Clauss kinetic assay), 183 ± 44 and 725 ± 199 mg per bag; VWF antigen content, 181 ± 53 and 218 ± 70 U per bag; VWF ristocetin cofactor activity, 168 ± 34 and 221 ± 65 U per bag; VWF collagen-binding activity, 164 ± 40 and 208 ± 71 U per bag; and fluid (plasma) volumes per bag, 21.3 ± 2.7 and 245 ± 29 mL.CONCLUSION: In contrast to other cryoprecipitable coagulation proteins, pFXIII is only mildly enriched in cryoprecipitate when compared with FFP (approx. two- to threefold). Although both products can provide effective pFXIII replacement, FFP may be preferred when infusion volume is not a major consideration and pFXIII concentrates are not available. VWF is substantially enriched in cryoprecipitate (approx. ninefold compared with its concentration in FFP), with VWF activity content exceeding that of FVIII by approximately 26 percent on average.
Transfusion 12/2008; 49(4):765 - 770. · 3.22 Impact Factor
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ABSTRACT: A previous investigation detailed the pathology of platelets in a family with the X-linked GATA-1 G208S mutation causing dyserythropoiesis and megathrombocytopenia. The present study has used ultrastructural immunocytochemistry, cytochemistry, and tannic acid staining to answer questions raised in the original investigation. Earlier studies, as well as ours, had shown that GATA-1 megathrombocytes are hypogranular, but did not definitively determine which organelles are decreased. Cytochemical localization of aryl sulfatase revealed that lysosomes were present in normal numbers, and the whole mount technique showed a normal frequency of dense bodies rich in arlenine nucleotides and serotonin. Thus alpha granules were the only organelles deficient in GATA-1 platelets. Tannic acid staining confirmed that the membranes wrapped around each other to form tubular inclusions come from elements of the dense tubular system. The unique tubular membrane inclusions in GATA-1 megathrombocytes, thought originally to derive from endoplasmic reticulum in the parent cell, were shown to be in direct continuity with elements of the surface connected open canalicular system (OCS), and to drive from the demarcation membrane system (DMS) of the megakaryocyte. Platelets in platelets and platelets in platelets in platelets were independent cells, and not derived by cytoplasmic sequestration in the enclosing macrothrombocytes. Fully spread GATA-1 platelets incubated with fibrinogen coated gold (Fgn/Au) particles before or after fixation bound as many Fgn/Au particles as normal spread platelets and moved the Fgn/Au- GPIIb/IIIa complexes from peripheral margins to cell centers and into channels of the OCS as efficiently. Exposure of spread normal platelets to bovine vWF resulted in coverage of the surface from edge to edge with multimers detected by anti-vWF antibody and protein A gold. Spread GATA-1 platelets bound very few vWF multimers, which were much smaller in size than those on normal spread cells, but were able to move then to cell centers. These findings support the concept that GATA-1 platelets are macrothrombocytes because they are not able to detach normally from each other during separation from megakaryocyte proplatelets. The marked decrease in the number and abnormal distribution of GPIb/IX receptors may play a role in GATA-1 megathrombocyte formation.
Platelets 10/2007; 18(6):436-50. · 1.85 Impact Factor
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ABSTRACT: Various mutations in the X-linked transcription factor, GATA-1, may result in dyserythropoietic anemia, macrothrombocytopenia and/or erythropoietic porphyria. The present study has carried out detailed ultrastructural studies of abnormal platelet morphology in one, previously described family with a GATA-1 G208S mutation. The ultrastructural investigations revealed a large proportion of their circulating platelets were hypogranular macrothrombocytes, resembling cells from patients with the Gray Platelet Syndrome. However, most of their platelets contained some alpha granules and a small number contained as many as are present in normal platelets. GATA-1 platelets from family members also contained tubular inclusions formed from elements of the dense tubular system like those observed in the Medich Giant Platelets Disorder. The unique pathology of the GATA-1 family platelets found in this study involved features never observed previously in normal or abnormal platelets. Many of their cells contained unusual flat, tubular membrane sheets, often in parallel association and differing from all other membrane systems in normal platelets and megakaryocytes. In some macrothrombocytes the unusual membranes appeared to isolate areas of cytoplasm. The sequestered areas were platelets within platelets. On rare occasion there were two platelets within one platelet, or, even more rarely, a platelet within a platelet within a platelet. Another unique feature, probably related to platelets within platelets, was the frequent attachment of non-activated platelets to each other to form macrothrombocytes. GATA-1 platelets within platelets and attached to platelets, as well as giant platelets, suggest that proplatelet formation may be abnormal, or that GATA-1 platelets are unable to pinch off from megakaryocyte proplatelets in a normal manner.
Platelets 07/2007; 18(4):273-83. · 1.85 Impact Factor
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ABSTRACT: Bleeding is a rare manifestation of lupus anticoagulant-antiphospholipid syndrome unless associated with coagulation factor deficiency, thrombocytopenia, or intrinsic vascular defect. The authors report the clinical and laboratory findings in a 16-year-old boy with potent lupus anticoagulant who initially presented with recurrent epistaxis, hematuria, and gastrointestinal bleeding. Lupus anticoagulant potently inhibited assay systems for coagulation factors, but levels of factors II, IX, and XI appeared to be decreased (2-5% of mean normal levels). Within 2 weeks after diagnosis, spontaneous subdural hematomas developed. During hemostatic therapy, including plasmapheresis and infusions of recombinant activated factor VII and activated prothrombin complex concentrate, an ischemic stroke developed. Subsequent multifocal recurrent ischemic strokes developed despite immunosuppression. This case shows that lupus anticoagulant or antiphospholipid antibodies can cause both hemorrhagic and thrombotic complications in the same patient and may, in some patients, have multiple target antigens (eg, coagulation factors II, IX, XI).
Journal of Pediatric Hematology/Oncology 08/2005; 27(7):403-7. · 1.16 Impact Factor
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ABSTRACT: To assess current laboratory practice and the performance of different reagent-instrument combinations for protein S testing, protein S results from the North American Specialized Coagulation Laboratory Association (NASCOLA) proficiency testing surveys for 2002 and the first half of 2003 were analyzed. A written survey of NASCOLA laboratories also was performed to further assess current laboratory practices for protein S testing. The free protein S antigen assays and the Diagnostica Stago Staclot protein S assay were extremely accurate in detecting a heterozygous type I protein S deficiency. Another functional protein S assay and most total protein S assays were less reliable, depending to some extent on the instrument. All assays used by NASCOLA laboratories appropriately identified normal protein S specimens. NASCOLA laboratories performed at least as well as European Concerted Action on Thrombosis laboratories in the proficiency tests. The results suggest that the diagnosis of heterozygous protein S deficiency may be problematic with some currently available assays. Many total protein S antigen assays do not add to the diagnosis and can be unreliable for protein S deficiency subtyping. Better standardization of functional and antigenic assays is needed.
American Journal of Clinical Pathology 06/2005; 123(5):778-85. · 2.60 Impact Factor
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ABSTRACT: Disorders of platelet function are important causes of abnormal bleeding that require laboratory tests for diagnosis. Currently there are limited guidelines on how to perform clinical testing for these disorders. The goal of our study was to obtain information on how disorders of platelet function are currently evaluated in clinical laboratories. Two patterns-of-practice surveys were distributed to laboratories of the North American Specialized Coagulation Laboratory Association (NASCOLA). The information collected was analyzed to determine practices and common problems. Forty-seven NASCOLA laboratories participated and 54% completed both surveys. The majority of the laboratories that responded performed more than 50 aggregation tests per year, mainly using platelet rich plasma based methodologies. A minority performed testing for platelet secretion and dense granule abnormalities. While platelet aggregation results were reviewed in various ways, laboratories most commonly issued a combined report containing quantitative values (% aggregation and/or slope) and a qualitative interpretation. Although laboratories used similar agonists for aggregation testing, the final agonist concentrations varied widely. Several approaches were also used to obtain reference intervals. Comments offered by the participants indicated that performing, and interpreting platelet function tests were challenging for many clinical laboratories. Although common practices have evolved, there is considerable variability in the diagnostic test procedures used by clinical laboratories to evaluate disorders of platelet function. These patterns-of-practice surveys illustrate a need for guidelines and recommendations for clinical laboratories performing tests of platelet function.
Thrombosis and Haemostasis 04/2005; 93(3):549-53. · 5.04 Impact Factor
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ABSTRACT: To assess the performance of 4 clotting assays for lupus anticoagulant (LA) detection, to determine the prevalence of LA and anticardiolipin antibodies (aCL), and to correlate LA and aCL prevalence with systemic disease and thrombosis.
We studied 664 consecutive patients at the Mayo Clinic in Rochester, Minn, who were referred for laboratory testing because of a clinical suspicion of LA or thrombophilia between June 25, 1990, and July 1, 1991.
Of 664 patients tested for LA, 584 also were tested for aCL. Of patients tested for both LA and aCL, 137 (235%) had positive results for one or both tests (13 [95%], LA-positive only; 76 [555%], aCL-positive only; and 48 [35.0%], positive for both). The dilute Russell viper venom time (DRVVT) was the most frequently positive LA assay (74% of the 61 patients with positive results for LA). Twenty-two patients (36.1% of the 61) had positive results for all 4 LA assays, whereas 21 (34.4% of the 61) had positive results for only 1 LA assay: activated partial thromboplastin time (3 patients [4.9%]), plasma clot time (5 patients [8.2%]), kaolin clot time (5 patients [8.2%]), or DRVVT (8 patients [13.1%]). Thromboembolism prevalence was not definitely associated with positive test results (LA only, aCL only, or LA plus aCL), nor was it strongly associated with aCL isotype or titer. Furthermore, thromboembolism prevalence was not increased when all LA assays were positive, although a history of deep venous thrombosis or pulmonary embolism was nonsignificantly associated with positive results for all 4 LA tests. The likelihood of having both LA- and aCL-positive test results was higher among patients with systemic lupus erythematosus (26 [19.0%] of 137 patients with positive results for one or both tests), but they had no more thrombotic events or fetal loss than other patients in our study group.
The DRVVT identified more patients with LA than the other LA tests, but more than 1 LA test was required to identify all patients with LA. Positive results were much more common for aCL than for LA. No single LA test or anticardiolipin isotype correlated with thrombosis or systemic disease in this population.
Mayo Clinic Proceedings 05/2004; 79(4):467-75. · 5.70 Impact Factor
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ABSTRACT: Sebastian platelet syndrome is a rare autosomal dominant disorder characterized by macrothrombocytopenia with granulocyte inclusions similar to those in patients with Fechtner platelet syndrome but without evidence of hereditary nephritis and sensorineural hearing loss that characterizes the latter. Although by light microscopy the granulocyte inclusions in these disorders appear morphologically similar to those found in May-Hegglin anomaly, another autosomal dominant macrothrombocytopenia, by electron microscopy the inclusions are distinct. Studies of platelet function usually suggest normal or near-normal platelet function, although mild bleeding symptoms can be associated with each of these disorders. We describe a 38-year-old woman and her 11-year-old daughter who presented with lifelong histories of mild thrombocytopenia and easy bruising. Detailed hemostatic studies showed prolonged bleeding times in the child and the mother, with the child having absent secondary wave platelet aggregation responses to epinephrine, also reflected by testing with the platelet function analyzer (PFA-100 device). The mother's hemostatic studies were normal including platelet aggregometry, PFA-100 testing, and platelet flow cytometry. By light microscopy the blood smears of both individuals showed neutrophil inclusions, and their platelets were mildly enlarged but were not giant. Electron microscopy showed the neutrophil inclusions seen in classic Sebastian platelet syndrome or Fechtner platelet syndrome. These 2 cases expand the description of Sebastian platelet syndrome to include individuals with large but not giant platelets and mild or minimal thrombocytopenia. The differential diagnosis of hereditary thrombocytopenias is reviewed briefly.
Mayo Clinic Proceedings 12/2003; 78(11):1416-21. · 5.70 Impact Factor
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ABSTRACT: The PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be superior to the bleeding time (BT) as a screening test of primary hemostasis. However evaluation of this device has been principally limited to selected populations. The study's aim was to determine testing performance in clinical practice, by comparing the PFA-100 to the BT for the identification of von Willebrand disease (VWD) and intrinsic platelet hypofunction. From 1998-2000, PFA-100 closure time (CT) for epinephrinecollagen (EPI) and ADP-collagen (ADP) cartridges and modified Ivy BTs were performed on outpatients referred for testing for suspected or known hemorrhagic diathesis (n = 346). Evaluation included assays of von Willebrand factor and platelet aggregometry in addition to platelet flow cytometry and electron microscopy when indicated. The normal distribution of PFA-100 CTs was determined using blood samples from 61 normal donors studied on 155 occasions. Results show that thirty-four patients met the diagnostic criteria for VWD and 31 patients were diagnosed with congenital or acquired intrinsic platelet hypofunction. The sensitivity of the PFA-100 for identification of VWD was significantly better (p < 0.01) than the BT with similar specificity. In contrast, the PFA-100 was comparable, but not superior to the BT for detecting platelet hypofunction. We conclude that the PFA-100 performance compares favorably to the BT for the identification of intrinsic platelet hypofunction in clinical practice with superior sensitivity for detecting VWD. Therefore, the PFA-100 could replace the BT for purposes of screening for VWD and intrinsic platelet hypofunction. When clinical suspicion is strong, testing should be supplemented with assays of von Willebrand factor and platelet aggregometry.
Thrombosis and Haemostasis 10/2003; 90(3):483-90. · 5.04 Impact Factor
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ABSTRACT: Acquired factor X (FX) deficiency is rare, but has been reported in diverse disease states, including systemic amyloidosis and respiratory infections. FX deficiency associated with lupus anticoagulant (LA) and a bleeding diathesis has not been previously reported. We report two patients both of whom presented with a severe bleeding diathesis after a preceding respiratory infection due to isolated FX deficiency associated with a LA. The FX deficiency and LA were transient. We conclude that patients with LA may rarely present with severe acquired FX deficiency. This may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.
British Journal of Haematology 06/2003; 121(4):639-42. · 4.94 Impact Factor
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Michelle A Elliott, William L Nichols,
Elizabeth A Plumhoff,
Stephen M Ansell,
Angela Dispenzieri,
Dennis A Gastineau,
Morie A Gertz,
David J Inwards,
Martha Q Lacy,
Ivana N M Micallef,
Ayalew Tefferi,
Mark Litzow
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ABSTRACT: To assess the activity of von Willebrand factor-cleaving protease (vWF-CP) in patients with thrombotic thrombocytopenic purpura (TTP) complicating bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT).
From March 1, 1999, to June 30, 2001, allogeneic and autologous hematopoietic stem cell transplantation was performed in 118 and 400 patients, respectively. We reviewed risk factors for development of posttransplantation TTP and measured vWF-CP activity during active TTP in 10 recipients.
The incidence of TTP after allogeneic and autologous transplantation was 6.8% (8/118) and 0.25% (1/400), respectively. Among the allogeneic transplant recipients, the incidence of TTP after nonmyeloablative (NMA) PBSCT, matched unrelated donor BMT, and sibling BMT or PBSCT was 15.4% (2/13), 11.8% (2/17), and 4.5% (4/88), respectively. Of the 10 patients with TTP, 9 (90%) had received extensive prior therapy, including autologous transplantation in both NMA recipients. Acute graft-vs-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in most affected patients. The vWF antigen level was elevated in all patients, and no patients showed evidence of vWF-CP deficiency. During active TTP, 6 patients had grade II-IV acute GVHD, 1 had extensive chronic GVHD, and 4 had cytomegalovirus viremia. Risk factor analysis for development of TTP showed that transplant type (NMA and matched unrelated donor) and source of stem cells (bone marrow vs peripheral blood stem cell) were significant.
Posttransplantation TTP was not found to be associated with severe vWF-CP deficiency. The elevated levels of vWF antigen are consistent with diffuse endothelial injury likely because of multiple interacting factors such as extensive prior therapy, GVHD, cyclosporine, and reactivation of cytomegalovirus. The disorder appears to be more frequent among patients with, or at risk for, acute GVHD, suggesting a possible role in the pathogenesis. Nonmyeloablative transplantation does not appear to confer a lesser risk, possibly for these reasons.
Mayo Clinic Proceedings 05/2003; 78(4):421-30. · 5.70 Impact Factor
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ABSTRACT: Acquired von Willebrand's disease or syndrome (AVWS) is a rare bleeding disorder distinguished from congenital von Willebrand's disease by age at presentation and absence of personal and family history of bleeding disorders. We report on 22 patients with AVWS seen over 25 years. Mean age at diagnosis was 61.3 years (range 38-86 years); most patients had a spontaneous or a post-operative hemorrhage at presentation. Gastrointestinal bleeding and epistaxis were the most common spontaneous symptoms. Bleeding time was prolonged in most patients, associated with marked reductions in plasma von Willebrand factor antigen and ristocetin cofactor activity. Plasma VWF multimer distribution was normal (type 1 pattern) in 5 patients, indeterminate (no multimers detectable) in 6 patients (type 3 pattern), and abnormal (decreased higher-molecular-weight multimers, type 2 pattern) in 11 patients. None of 17 patients tested had an inhibitor of ristocetin cofactor activity. An underlying malignant or benign hematologic disease was found in 18 patients, and 1 patient had Crohn's disease. Desmopressin was effective in only half the patients so treated, but all patients responded to treatment with VWF-containing concentrates. Resolution of AVWS occurred with therapy of lymphoma (1 patient) and chronic lymphocytic leukemia (1 patient). Sixteen patients were alive at last follow-up; no deaths were related to bleeding. AVWS may be more prevalent than has been appreciated; we estimate up to 0.04%. Awareness of the existence of AVWS is essential for diagnosis and appropriate management. Therapy of associated diseases may improve the bleeding disorder.
American Journal of Hematology 05/2003; 72(4):243-7. · 4.67 Impact Factor
