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2.
J Med Case Rep ; 1: 175, 2007 Dec 07.
Article in English | MEDLINE | ID: mdl-18067664

ABSTRACT

INTRODUCTION: Iron deficiency anemia is commonly associated with thrombocytosis, although thrombocytopenia has been reported in occasional patients with iron-deficiency anemia. Much less common is the development of thrombocytopenia following replenishment of iron stores. CASE PRESENTATION: We present the unusual case of a 39 year old African American female Jehovah's Witness who presented with a 10 month history of menorrhagia and pancytopenia. Laboratory investigations confirmed a severe iron deficiency. Since blood transfusion was unacceptable to her, she was started on intravenous iron replacement therapy. This precipitated a sudden drop in both her platelet and white blood cell counts. Histopathological examination of the bone marrow revealed a hypercellular marrow with orderly trilineage hematopoiesis, iron deficiency anemia, granulocytic hyperplasia, and mild megakaryocytic hypoplasia. Both her white blood cell and platelet counts recovered uneventfully with continuing iron supplementation. The possible mechanism for this phenomenon is discussed in this report. CONCLUSION: This case illustrates two rather uncommon associations of a very common problem. Severe iron deficiency anemia may be associated with pancytopenia and iron replacement may cause a transient decline in megakaryopoiesis and leukopoiesis. Severe iron deficiency should be added to the list of conditions leading to thrombocytopenia.

3.
J Thromb Thrombolysis ; 23(2): 155-8, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17131175

ABSTRACT

INTRODUCTION: Dysfibrinogenemia is a disorder of fibrinogen structure and is associated with a functional abnormality. Since fibrinogen is a key component of both the procoagulant and fibrinolytic pathways, defects in fibrinogen function can be associated with increased risk for both hemorrhage and thrombosis. Management of patients with dysfibrinogenemia and a thrombotic tendency usually involves long-term anticoagulation. CASE: A 36-year-old male with relapsed nodular sclerosing Hodgkin's was found to have a prolonged prothrombin time, low fibrinogen activity and a normal fibrinogen antigen during evaluation for a hematopoietic peripheral blood stem cell transplant. His past medical history was significant for an acute myocardial infarction and two episodes of acute pancreatitis. His father had dysfibrinogenemia complicated by multiple thrombotic episodes. A trans-esophageal echocardiogram revealed two thrombi, one each in the superior vena cava and the descending aorta. He was treated with enoxaparin and received peripheral blood stem cell transplantation. An effort was made to maintain his fibrinogen activity levels at 200 mg/dL using cryoprecipitate. A month following the transplant he developed a new thrombus in the right internal jugular vein, while on enoxaparin and he was started on argatroban and cryoprecipitate followed by fondaparinux. A repeat echocardiogram six weeks later demonstrated that the burden of thrombus both in the right atrium and descending aorta was significantly lower. DISCUSSION: This is the first case report of a patient with dysfibrinogenemia undergoing peripheral blood stem cell transplantation. Conventional anticoagulant therapy and cryoprecipitate seem to be a reasonable management strategy to prevent thrombosis in a patient with dysfibrinogenemia and a thrombophilic tendency. Secondly, fondaparinux can be used in cases of failure of therapy with low molecular weight heparins and may actually be superior to low molecular weight heparins, especially in patients with dysfibrinogenemia.


Subject(s)
Anticoagulants/therapeutic use , Enoxaparin/therapeutic use , Fibrinogens, Abnormal/drug effects , Hematopoietic Stem Cell Transplantation/methods , Hodgkin Disease/complications , Thrombosis , Adult , Factor VIII/therapeutic use , Fibrinogen/analysis , Fibrinogen/therapeutic use , Fibrinogens, Abnormal/adverse effects , Graft Survival , Hodgkin Disease/therapy , Humans , Male , Thrombosis/blood , Thrombosis/prevention & control
5.
Crit Care Med ; 32(10): 1990-6, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15483405

ABSTRACT

BACKGROUND: The treatment of choice for central venous access device (CVAD) occlusion is intracatheter thrombolysis, which has been reported to reestablish patency in up to 80% of cases. However, these salient results have only been achieved in highly selected CVAD subgroups such as nontunneled devices in adult patients, devices with recent occlusion, and in partially occluded devices through which fluid can still be infused (withdrawal occlusions). Less is known about the success of intracatheter thrombolysis in the broader range of CVAD malfunction encountered in clinical practice, especially in those devices that are totally occluded. OBJECTIVE: This multiple-center, open-label study was performed to test the hypothesis that a new recombinant urokinase (r-UK, urokinase alfa) is safe and effective in reestablishing patency in a large unselected cohort of occluded CVADs. METHODS: Pediatric and adult patients with any type of CVAD occlusion of any duration were treated with 5000 IU/mL intracatheter r-UK. Lumen patency was assessed after 5, 15, and 30 mins; a second dose of r-UK was instilled if the catheter remained occluded after 30 mins. RESULTS: A total of 903 r-UK instillations were performed in 878 patients (age range, 16 days to 96 yrs). Overall, instillation of r-UK successfully restored total catheter patency (all treated lumens) to 75% of CVADs (681 of 902). Patency was restored to at least one occluded lumen in 79% of devices (712 of 902). Patency was restored equally in catheters with total occlusion (76%) as in catheters with only withdrawal occlusion (75%). The median +/- sd time to patency was 15 +/- 20.8 mins (range, 5-203 mins). CONCLUSION: The use of a new r-UK, 5000 IU/mL, is safe and effective for the restoration of patency to occluded CVADs.


Subject(s)
Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Plasminogen Activators/therapeutic use , Thrombosis/drug therapy , Urokinase-Type Plasminogen Activator/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Child , Child, Preschool , Cohort Studies , Equipment Failure , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Thrombolytic Therapy/methods , Thrombosis/etiology , Treatment Outcome
6.
Thromb Haemost ; 92(3): 575-82, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15351854

ABSTRACT

The interval occlusion of central venous access devices (CVADs) remains a significant clinical problem, often requiring re-intervention for catheter exchange or replacement. The purpose of this Phase 3, multi-center, double-blinded study was to test the hypothesis that instillation of recombinant urokinase (r-UK) 5000 IU/ml is superior to placebo in restoring total catheter patency to an unselected cohort of occluded CVADs. After obtaining informed consent, adult and pediatric patients with occluded, non-hemodialysis CVADs of any duration or type were randomized (2 : 1) to receive either r-UK 5000 IU/ml or placebo instilled into all occluded lumens of their catheter. Catheter function was assessed at 5, 15 and 30 min after the first instillation. If the catheter remained occluded after 30 min, a second dose was instilled with repeat assessments at 5, 15 and 30 min. The primary efficacy variable was the restoration of catheter function to all treated lumens (i.e., total catheter patency) after one or two instillations. Catheters that were not successfully recanalized after two instillations were allowed to receive up to two instillations of open-label r-UK administered in the same manner. The primary safety variable was the occurrence of hemorrhagic and non-hemorrhagic events within 72 hr after instillation. A total of 180 patients were enrolled at 43 sites in the United States and Canada. Most patients were adults, although 20% were

Subject(s)
Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Graft Occlusion, Vascular/drug therapy , Urokinase-Type Plasminogen Activator/administration & dosage , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Double-Blind Method , Female , Hemorrhage , Humans , Infant , Kinetics , Male , Middle Aged , Placebos , Recombinant Proteins , Urokinase-Type Plasminogen Activator/adverse effects
8.
J Thromb Thrombolysis ; 15(3): 227-32, 2003 Jun.
Article in English | MEDLINE | ID: mdl-14739633

ABSTRACT

New paradigms for the diagnosis, prophylaxis, acute treatment, and ongoing management of patients with venous thromboembolic disease (VTE), a better understanding of the genotypic and phenotypic mechanisms of thrombophilic states, and the possibility of a greatly expanded armamentarium of antithrombotic therapies are necessitating a more formalized and systematic approach to VTE management. This has required many US healthcare institutions to develop piecemeal approaches in management models for VTE utilizing local champions from a variety of subspecialties. Development of a formalized Clinical Thrombosis Center from an already established Anticoagulant Management Service utilizing a clinical thrombologist, a new role for a physician who has developed expertise in anticoagulation and VTE management, presents a new paradigm in which this disease may be approached at a formalized, institutional level. Thus the clinical thrombologist working through a Clinical Thrombosis Center can develop a system-of-care approach to link the rapid advances in the field of thromboembolism to clinical applications, formulate evidence-based disease management guidelines, and conduct patient-oriented translational clinical research in VTE.


Subject(s)
Cardiology/organization & administration , Hospital Units/organization & administration , Institutional Practice , Patient Care Management , Venous Thrombosis/therapy , Disease Management , Hematology/organization & administration , Humans , Practice Guidelines as Topic , Thromboembolism/therapy , United States , Workforce
9.
Crit Care Med ; 30(5 Suppl): S257-62, 2002 May.
Article in English | MEDLINE | ID: mdl-12004245

ABSTRACT

OBJECTIVE: To review the data demonstrating that central nervous system, pulmonary, and hepatic dysfunctions during hematopoietic stem cell transplantation have similar laboratory correlates and clinical outcomes, suggesting that they are individual organ manifestations of a systemic disorder at presentation, a disorder similar to the multiple organ dysfunction syndrome seen in other populations of critically ill patients. DATA SOURCES AND STUDY SELECTION: Reports of clinical research studies on the natural history and laboratory correlates of central nervous system, pulmonary, and hepatic dysfunction (generally manifesting as the syndrome of hepatic veno-occlusive disease) during hematopoietic stem cell transplantation. DATA EXTRACTION AND SYNTHESIS: During hematopoietic stem cell transplantation, pulmonary dysfunction (manifesting as hypoxia), central nervous system dysfunction (detected by alteration of the Mini-Mental Status Exam), and hepatic dysfunction (presenting as the syndrome of hepatic veno-occlusive disease) are all associated with significant decreases in the levels of antithrombin III and protein C and an increase in the platelet transfusion requirement. Each of these three organ dysfunctions is associated with a high likelihood of being followed by the other two and, eventually, death. Patients with these organ dysfunctions have higher levels of interleukin-6, interleukin-10, and tumor necrosis factor-alpha than patients who never develop these complications. Mortality rates for patients with these organ dysfunctions vary from 15% in patients with only one organ dysfunction to 100% in patients who have progressed to all three. Patients who develop none of these organ dysfunctions have a mortality rate that approaches zero. CONCLUSIONS: Central nervous system, pulmonary, and hepatic dysfunctions are intimately involved in the mortal complications of hematopoietic stem cell transplantation. Because these organ dysfunctions have similar correlates and similar outcomes, the hypothesis that they are individual parts of a systemic disorder is proposed. The additional observation that these organ dysfunctions are associated with abnormally high levels of inflammation-related cytokines raises the possibility that their pathogenesis is similar to that of multiple organ dysfunction syndrome in other populations of critically ill patients.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Multiple Organ Failure , Antithrombin III/metabolism , Central Nervous System Diseases/blood , Central Nervous System Diseases/etiology , Central Nervous System Diseases/mortality , Hepatic Veno-Occlusive Disease/blood , Hepatic Veno-Occlusive Disease/etiology , Hepatic Veno-Occlusive Disease/mortality , Humans , Interleukin-6/blood , Logistic Models , Lung Diseases/blood , Lung Diseases/etiology , Lung Diseases/mortality , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Protein C/metabolism , Tumor Necrosis Factor-alpha/metabolism
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