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1.
Thromb Res ; 161: 43-51, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29178990

RESUMO

INTRODUCTION: Thrombotic storm (TS) presents as a severe, acute thrombotic phenotype, characterized by multiple clotting events and frequently affecting younger adults. Understanding the extensive hypercoagulation of an extreme phenotype as TS will also provide insight into the pathogenesis of a wider spectrum of thrombotic disorders. MATERIAL AND METHODS: We completed whole exome sequencing on 26 TS patients, including 1 multiplex family, 13 trios and 12 isolated TS patients. We examined both dominant and recessive inheritance models for known thrombotic factors as well as performed a genome-wide screen. Identified genes of interest in the family and trios were screened in the remaining TS patients. Variants were filtered on frequency (<5% in 1000 genomes), conservation and function in gene and were annotated for effect on protein and overall functionality. RESULTS: We observed an accumulation of variants in genes linked to chondroitin sulfate (CS), but not heparan sulfate metabolism. Sixteen conserved, rare missense and nonsense variants in genes involved in CS metabolism (CHPF, CHPF2, CHST3, CHST12, CHST15, SLC26A2, PAPSS2, STAB2) were identified in over one-third of the TS patients. In contrast, we identified only seven variants in known thrombosis genes (including FV Leiden). CONCLUSIONS: As CS has multiple functions in the glycocalyx protecting the endothelial cells, reduced availability of CS could diminish the normal control mechanisms for blood coagulation, making these CS metabolism genes strong potential risk factors for TS. Overall, no single gene was identified with strong evidence for TS causality; however, our data suggest TS is mediated by an accumulation of rare pro-thrombotic risk factors.


Assuntos
Sulfatos de Condroitina/metabolismo , Trombose/genética , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/metabolismo , Adulto Jovem
2.
Curr Opin Hematol ; 22(5): 420-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26248002

RESUMO

PURPOSE OF REVIEW: Blood coagulation exists to halt excessive blood loss. It is paradoxical that surgery and trauma simultaneously represent major risk factors for both hemorrhagic and thrombotic complications. A summary of the available evidence used to guide contemporary approaches to perioperative care will be reviewed. RECENT FINDINGS: Although the advent of factor-specific products has safely allowed for intervention on patients with congenital hemostatic defects, the presence of an increasingly complex surgical population (chronic liver disease, traumatic injuries, and requirements for chronic anticoagulation) has renewed concerns about hemorrhagic risks. However, the past three decades of clinical sciences have supported a re-emphasis on the prevention of venous thromboembolism (VTE), a major cause of morbidity and mortality in hospitalized surgical patients. There is now an abundance of data confirming the robust risk:benefit ratio of antithrombotic prophylaxis in the vast majority of surgical patients, regardless of their medical comorbidities. SUMMARY: Perioperative hemorrhage is a natural risk of any surgical intervention and deserves careful evaluation and prompt intervention. However, in order to support ongoing efforts in the prevention of medical errors, the application of evidence-based guidelines for the prophylaxis of VTE in surgical patients must become a standard part of daily practice.


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Hemorragia/prevenção & controle , Hemostasia Cirúrgica/métodos , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/complicações , Transfusão de Sangue/métodos , Fibrinolíticos/efeitos adversos , Humanos , Assistência Perioperatória , Plasma , Medição de Risco/métodos , Fatores de Risco , Procedimentos Cirúrgicos Operatórios
3.
Blood ; 126(11): 1285-93, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26179082

RESUMO

Catastrophic thrombotic syndromes are characterized by rapid onset of multiple thromboembolic occlusions affecting diverse vascular beds. Patients may have multiple events on presentation, or develop them rapidly over days to weeks. Several disorders can present with this extreme clinical phenotype, including catastrophic antiphospholipid syndrome (APS), atypical presentations of thrombotic thrombocytopenic purpura (TTP) or heparin-induced thrombocytopenia (HIT), and Trousseau syndrome, but some patients present with multiple thrombotic events in the absence of associated prothrombotic disorders. Diagnostic workup must rapidly determine which, if any, of these syndromes are present because therapeutic management is driven by the underlying disorder. With the exception of atypical presentations of TTP, which are treated with plasma exchange, anticoagulation is the most important therapeutic intervention in these patients. Effective anticoagulation may require laboratory confirmation with anti-factor Xa levels in patients treated with heparin, especially if the baseline (pretreatment) activated partial thromboplastin time is prolonged. Patients with catastrophic APS also benefit from immunosuppressive therapy and/or plasma exchange, whereas patients with HIT need an alternative anticoagulant to replace heparin. Progressive thrombotic events despite therapeutic anticoagulation may necessitate an alternative therapeutic strategy. If the thrombotic process can be controlled, these patients can recover, but indefinite anticoagulant therapy may be appropriate to prevent recurrent events.


Assuntos
Trombose/terapia , Adolescente , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/terapia , Doença Catastrófica , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Troca Plasmática , Gravidez , Púrpura Trombocitopênica Trombótica/terapia , Síndrome , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia , Trombose/diagnóstico , Trombose/etiologia
4.
Expert Rev Hematol ; 5(6): 653-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23216595

RESUMO

Thrombotic storm represents an extreme prothrombotic phenotype, characterized by multiple thrombotic events affecting diverse vascular beds occurring over a brief period of time. Thrombotic events involve venous and arterial circulation, including unusual locations, such as cerebral sinus venous thrombosis, intra-abdominal thromboembolic occlusions and microvascular events. Some patients will have antiphospholipid antibodies, but a significant number have no identifiable hypercoagulable state. The mainstay of treatment consists of anticoagulant therapy, although some patients appear to benefit from the addition of immunomodulatory therapies. Other disorders that share this thrombotic storm phenotype include catastrophic antiphospholipid syndrome, spontaneous heparin-induced thrombocytopenia and similar aggressive clinical disorders. Ongoing studies are focused on identifying underlying genetic factors that may predispose patients to develop this extreme clinical phenotype.


Assuntos
Anticoagulantes/uso terapêutico , Trombofilia/tratamento farmacológico , Trombofilia/patologia , Trombose/tratamento farmacológico , Trombose/patologia , Humanos
6.
Am J Med ; 124(4): 290-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21435416

RESUMO

Physicians periodically encounter patients with an extraordinarily accelerated course of hypercoagulability who develop thromboses in multiple organ systems over days to weeks. Such patients may harbor underlying hypercoagulable clinical conditions, but their clinical course sets them apart from most patients with similar risk factors. Underlying triggers of "thrombotic storm" include pregnancy, inflammation, trauma, surgery, and infection. Aggressive anticoagulant therapy may control thrombotic storm, yet thrombotic storm may resume with even brief interruptions of anticoagulant therapy. The authors of this communication formed the Thrombotic Storm Study Group in order to identify clinical characteristics of such patients, thus constructing preliminary criteria to better define, identify, and study the course of patients deemed to have thrombotic storm. The characteristics culled from these 10 patients are: younger age (oldest was 38 years old at time of presentation); at least 2 arterial or venous (or both) thromboembolic events, typically in unusual sites with or without microangiopathy; unexplained recurrence; and frequently proceeded by a trigger. The following characteristics were not used in defining thrombotic storm: underlying malignancies; use of acute myocardial infarction as a defining arterial event in the setting of established coronary artery disease; use of cocaine; thrombotic complications expected with various intravascular devices; known paroxysmal nocturnal hemoglobinuria or myeloproliferative disorders; severe trauma; and premorbid conditions.


Assuntos
Anticoagulantes/uso terapêutico , Trombofilia/complicações , Trombofilia/diagnóstico , Trombose/diagnóstico , Trombose/etiologia , Humanos , Trombofilia/tratamento farmacológico , Trombose/tratamento farmacológico
7.
Blood ; 117(1): 39-44, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-20980677

RESUMO

Thrombosis of superficial veins has long been regarded as a benign disorder. If patients with a clinical diagnosis of superficial venous thrombosis (SVT) are thoroughly evaluated, the degree and extent of thrombosis in patients with SVT are characteristically underestimated (∼ 75% of the time) and such patients have coexistence (∼ 25% of the time) of, and/or rapid progression (∼ 10% of the time) to, systemic venous thromboembolism (VTE). Pulmonary embolism (PE; ∼ 25% of the time) and death (∼ 1% of the time) occur. Contributory risk factors for SVT are the same for VTE. Treatment of patients' SVT with parenteral anticoagulants appears to be both efficacious and certainly safe. I regard most patients with a clinical diagnosis of SVT the same as those with VTEs. Systemic anticoagulant therapy of patients with a clinical diagnosis of SVT obviates extensive imaging and laboratory workup and may be cost effective while encompassing treatment of any unknown concomitant thromboses with only low risk for hemorrhage. This decision is especially clear in those patients with known hypercoagulability. Patients without clinical risk factors are at lower risk to develop VTE complications and might be those who can be simply observed.


Assuntos
Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Humanos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Fatores de Risco , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-20008204

RESUMO

Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.


Assuntos
Coagulação Intravascular Disseminada/complicações , Trombocitopenia/etiologia , Trombose/etiologia , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Idoso , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/fisiopatologia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Evolução Fatal , Fondaparinux , Doenças Transmitidas por Alimentos/complicações , Hemorragia/etiologia , Heparina/uso terapêutico , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Polissacarídeos/uso terapêutico , Complicações Pós-Operatórias/etiologia , Tromboflebite/tratamento farmacológico , Tromboflebite/etiologia , Vibrioses/complicações , Vibrio vulnificus , Adulto Jovem
9.
J Thromb Thrombolysis ; 28(4): 500-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19521667

RESUMO

Inferior vena cava (IVC) thrombosis is a complication that occurs in 1-32% of patients inserted with IVC filters (IVCF). Deployment of the filter in the suprarenal position is advocated in certain clinical conditions, and some reports suggest a higher incidence of renal complications in that position, especially among patients with malignancy. We report a case of acute kidney injury (AKI) due to acute thrombosis of a suprarenal IVCF, which was successfully treated with systemic thrombolytic therapy. We also provide a review of the literature in regard to the indications, complications, and outcomes of suprarenal IVCF. Suprarenal IVCF placement should be performed rarely, and then only after careful evaluation of the underlying renal function, and likely should be avoided in patients with malignancy and known hypercoagulable state. Systemic thrombolytic therapy is a feasible treatment option for acute thrombotic episodes of IVCF, assuming it is diagnosed early and there are no known contraindications.


Assuntos
Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Terapia Trombolítica , Filtros de Veia Cava/efeitos adversos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Doença Aguda , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica/métodos
10.
J Thromb Thrombolysis ; 23(3): 223-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17221331

RESUMO

BACKGROUND: Patients with hypercoagulability may thrombose visceral veins with resultant portal hypertension, esophagogastric varices, and hemorrhage. The role of chronic oral anticoagulant therapy in such patients is unclear. On the one hand, such patients are prone to significant hemorrhage and thus anticoagulant therapy may seem contraindicated. On the other hand, because the causal pathophysiology is typically hypercoagulability, it would seem rational to treat these patients with chronic anticoagulant therapy in order to both prevent other visceral and systemic thromboses and perhaps, over time, reduce the degree of portal hypertension. Experience and poor prognosis associated with the more common portal hypertension due to hepatic cirrhosis may bias judgment. METHODS: We retrospectively reviewed the course of chronic oral anticoagulant therapy regarding both the safety and effectiveness using our long-term follow-up of a cohort of seven patients with visceral thrombosis resulting in extrahepatic non-cirrhotic portal hypertension. RESULTS: Seven consecutive patients encountered over the past 19 years were observed for 78 patient-years, the first 14 patient-years prior to anticoagulant therapy and the latter 64 patient-years on oral anticoagulant therapy. No patients rethrombosed either visceral or systemic vessels while on oral anticoagulant therapy. There were no fatal or serious hemorrhagic events on oral anticoagulant therapy; in fact, upper gastrointestinal bleeding decreased from 1.2 to 0.2 bleeds/year. The endoscopic grade of esophageal varices decreased in four of five patients who underwent serial endoscopy, and platelet counts increased in all seven patients. CONCLUSIONS: Chronic oral anticoagulant therapy is safe and not associated with an increase in upper gastrointestinal bleeding in such patients. Additionally, and by inference, perhaps in conjunction with the natural history of portal hypertension, such therapy is possibly effective in reducing portal hypertension in patients with hypercoagulability-induced extrahepatic portal hypertension.


Assuntos
Anticoagulantes/uso terapêutico , Trombose/tratamento farmacológico , Vísceras/irrigação sanguínea , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Feminino , Hemorragia/etiologia , Humanos , Hipertensão Portal/etiologia , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombofilia/complicações , Trombose/complicações , Trombose/terapia , Varfarina/uso terapêutico
12.
Cleve Clin J Med ; 72(5): 377-8, 383-5, 390 passim, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15929452

RESUMO

Disseminated intravascular coagulation (DIC) is a manifestation of an underlying pathologic process such as cancer, infection, trauma, or obstetric catastrophe. It can manifest as thrombosis, bleeding, or both. To succeed, treatment must address the underlying cause.


Assuntos
Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/terapia , Coagulação Sanguínea , Coagulação Intravascular Disseminada/etiologia , Embolia Amniótica/etiologia , Feminino , Humanos , Infecções/complicações , Masculino , Neoplasias/complicações , Guias de Prática Clínica como Assunto , Gravidez , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Ferimentos e Lesões/complicações
14.
Chest ; 127(3): 922-7, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15764777

RESUMO

BACKGROUND: The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement. METHODS: Over an 11-year period (ie, 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated. RESULTS: The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n = 65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n = 75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n = 70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels. CONCLUSIONS: Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy.


Assuntos
Anticoagulantes/administração & dosagem , Tromboembolia/prevenção & controle , Varfarina/administração & dosagem , Administração Oral , Anticoagulantes/efeitos adversos , Estudos de Viabilidade , Heparina/administração & dosagem , Humanos , Coeficiente Internacional Normatizado , Fatores de Risco , Varfarina/efeitos adversos
15.
Am J Hematol ; 76(1): 69-73, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15114601

RESUMO

Thrombocytopenia is an uncommon but serious consequence of heparin administration. Occasionally patients with massive acute venous thromboembolism (VTE) will develop thrombocytopenia. As heparin or some thrombin inhibitor is strongly indicated in acute VTE, it is important to distinguish this event from heparin-induced thrombocytopenia (HIT). Four patients are presented who developed thrombocytopenia so early in their course of VTE and/or therapy with heparin that HIT was considered unlikely. The mean nadir platelet count for these four patients was 60,000/microl occurring at a mean time of 18 hr after the initiation of heparin therapy. Because of strong indications to continue heparin for their acute VTE in the face of a very low likelihood that they did have HIT, heparin was continued with excellent results and resolution of the thrombocytopenia. The literature of this subject is reviewed. Thrombocytopenia following VTE is actually rather common, but it is usually milder than in these four cases. In some cases such as these four, the thrombocytopenia can be sudden and rather severe causing diagnostic confusion with HIT.


Assuntos
Heparina/efeitos adversos , Trombocitopenia/diagnóstico , Tromboembolia/complicações , Trombose Venosa/complicações , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Trombocitopenia/induzido quimicamente , Trombocitopenia/etiologia
16.
Arch Pathol Lab Med ; 126(11): 1382-6, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12421145

RESUMO

OBJECTIVES: To review the literature for conditions, diseases, and disorders that affect activity of the contact factors, and further to review the literature for evidence that less than normal activity of any of the contact factors may be associated with thrombophilia. DATA SOURCES: MEDLINE search for English-language articles published from 1988 to 2001 and pertinent references contained therein, as well as search of references in recent relevant articles and reviews. STUDY SELECTION: Relevant clinical and laboratory information was extracted from selected articles. Meta-analysis was not feasible because of heterogeneity of reports. DATA EXTRACTION AND SYNTHESIS: Evidence for association of altered levels of the contact factors and thrombophilia was sought. A wide variety of disorders is associated with decreased activity of the contact factors; chief among these disorders are liver disease, hepatic immaturity of newborns, the antiphospholipid syndrome, and, for factor XII, being of Asian descent. These disorders are more common than homozygous deficiency. The few series and case reports of thrombophilic events in patients homozygous for deficiency of contact factors are not persuasive enough to support causality. The apparent association between levels consistent with heterozygosity (40%-60% of normal) of any of the contact factors (but especially factor XII) in persons with antiphospholipid antibodies appears to be due to falsely decreased in vitro activity levels of these factors, which are normal on antigenic testing. The apparent association with thrombosis is better explained by the antiphospholipid syndrome than by the modest reduction of the levels of contact factors. CONCLUSIONS: Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes.


Assuntos
Fator XIa/fisiologia , Trombofilia/diagnóstico , Coagulação Sanguínea/fisiologia , Testes de Coagulação Sanguínea , Fator XII/fisiologia , Deficiência do Fator XII/diagnóstico , Deficiência do Fator XII/etiologia , Deficiência do Fator XII/fisiopatologia , Humanos , Cininogênio de Alto Peso Molecular/deficiência , Cininogênio de Alto Peso Molecular/fisiologia , Guias de Prática Clínica como Assunto , Pré-Calicreína/deficiência , Pré-Calicreína/fisiologia , Trombofilia/complicações , Trombofilia/fisiopatologia
19.
Philadelphia; W.B. Saunders Company; 2002. 617 p. graf, ilus, tab.
Monografia em Inglês | Sec. Munic. Saúde SP, AHM-Acervo, TATUAPE-Acervo | ID: sms-11169
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