Pathophysiology, clinical manifestations and therapy of consumption-coagulopathy (“Verbrauchskoagulopathie”)

Lasch, H. G.; Heene, D. L.; Huth, K; Sandritter, W.

doi:10.1016/0002-9149(67)90062-8

Cited by 164 publications

(40 citation statements)

References 30 publications

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“…"Latent coagulation" 27 with presence of soluble fibrin complexes in the circulation might serve as a defense mechanism, leading to increased plasminogen activation, clearance of fibrin deposits, reduction of fibrinogen levels, and generation of fibrinogen degradation products acting as "endogenous anticoagulants." …”

Section: Discussionmentioning

confidence: 99%

Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model

Elmas

Suvajac

Jilma

et al. 2010

Blood

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Disseminated intravascular coagulation in sepsis is associated with microvascular thrombosis and organ dysfunction. It was expected that prothrombotic disposition such as factor V Leiden (FVL) mutation would worsen clinical outcome. Astonishingly, clinical trial and animal experimental data indicate that FVL can be associated with improved survival. This study investigated the effect of FVL on the response to endotoxin of the coagulation and fibrinolytic system in humans. Fourteen healthy male subjects without FVL and 15 healthy males with heterozygous FVL received an intravenous bolus dose of endotoxin, 2 ng/kg of body weight. Blood samples were drawn before and 1, 2, 4, 6, and 24 hours after administration of the endotoxin. Injection of endotoxin led to a more pronounced increase in soluble fibrin in patients with FVL than in controls. Patients with FVL displayed a more sustained increase in plasmin-plasmin inhibitor complex after 4, 6, and 24 hours. Patients with FVL mutation also displayed higher levels of D-dimer and fibrinogen-fibrin degradation products in plasma after 24 hours. Patients with FVL generate higher levels of soluble fibrin, which may serve as cofactor in tissue plasminogen activatorinduced plasminogen activation, leading to a more sustained activation of fibrinolysis with production of more fibrinogenand fibrin-degradation products. (Blood. 2010;116(5):801-805) IntroductionReplacement of Arg506 with Gln in coagulation factor V (the factor V Leiden [FVL] mutation) 1 results in the loss of an important cleavage site for activated protein C (aPC). Factor Va carrying the FVL mutation is less sensitive to inactivation by aPC. In addition, FVL may display an impaired cofactor function in the degradation of factor VIIIa by aPC. FVL predisposes for the development of venous thrombosis. 2 The high prevalence of FVL in the European population 3 indicates some survival advantage, which might be related to less blood loss on injury or childbirth or to improved wound healing. 4 This may be a consequence of enhanced fibrin formation due to the impaired inactivation of factor Va.Presence of disseminated intravascular coagulation (DIC) in sepsis is associated with an adverse outcome. 5 DIC may lead to microvascular thrombosis, causing multiple organ dysfunctions, and it is conceivable that a prothrombotic disposition such as FVL would be associated with an increased rate of fibrin disposition, causing organ dysfunction and death in sepsis.Astonishingly, data from the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) and Extended Evaluation of Recombinant Human Activated Protein C in Severe Sepsis (ENHANCE) trials indicate that the FVL mutation might be associated with improved survival in severe sepsis. 6,7 In the PROWESS trial, mortality of patients with severe sepsis with heterozygous FVL was 15.6%, compared with 31.0% in patients without FVL in the patient group not treated with recombinant aPC (Drotrecogin alfa [activated]). In patients treated with Drotrecogin alfa (...

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Section: Discussionmentioning

confidence: 99%

Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model

Elmas

Suvajac

Jilma

et al. 2010

Blood

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“…One of the earliest reports implicating Gram negative and septicaemia in consumption coagulopathy (DIC) was published by Lasch et al in 1967 [7]. Siegal et al [8] observed that out of 118 patients of DIC, 21 were due to Gram negative septicaemia.…”

Section: Gram Positive Vis Gram Negative Infectionmentioning

confidence: 99%

“…D espite a number of studies on coagulation parameters in fulminant septicemia [1][2][3]; experimental infection [4][5][6]; and DIC [7][8][9]; there is a paucity of literature regarding coagulation abnormalities in uncomplicated acute infection. Abnormalities ranging from a rapidly fatal DIC to a slight elevation in the levels of fibrin/fibrinogen degradation products (FOP) are seen in acute infections and septicaemia.…”

Section: Introductionmentioning

confidence: 99%

DIAGNOSING DISSEMINATED INTRAVASCULAR COAGULATION IN ACUTE INFECTION : CAN WE DO WITHOUT FDP & D-DIMER

Arora

Mishra

Nair

et al. 2002

Medical Journal Armed Forces India

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Alterations in coagulation prome viz. platelet count, prothrombin time (PT), partial thromboplastin time with kaolin (PI'TK), thrombin time (TT) and fibrinogen were studied in 96 patients (73 males and 23 females) of acute infections. Fibrinlfibrinogen degradation products (FOP) level >251-lK fibrinogen equivalent unit (FEU)/ml along-with D-dimer >1.0J.tg FEU/ml was considered criteria for diagnosis of dJsseminated intravascular coagulation (DIC). Normal values were established using plasma from 12 healthy voluntary blood donors. Out of these 96 patients, 15 had infection with Gram positive bacteria, 23 with Gram negative bacteria and 38 with Dengue. In 20 patients, nature of infection was not defined. Mean platelet count per cubic millimetre was 2.14 lac In Gram positive infection and 1.74 lac in Gram negative infection (p=O.07). There was no signiftcant dill'erence in other coagulation parameters In Gram positive and Gram negative Infection. Platelet counts were low in 71% of Dengue patients but there was no signlftcant alteration in PT, PI'TK and TT. None of the Dengue patients had hypoflbrinogenemia or DIC though hyperftbrlnogenemla was present In 21% of Dengue patients. 20 patients had features of septicemia (Gram +ve 7, Gram -ve 8, undefined 5); 10 bad concomitant DIC. DIC was present in additional 4 patients of acute infection without septicemia. P'ITK was raised in 60% of the septicemia patients. 20 out of 82 non-DIC acute infection patients had subnormal P'ITK. Commonest alteration In 14 DIC patients was raised P'ITK with a sensitivity of 78.6% and speclOclty of 81.7%. Low fibrinogen levels though spedftc for DIC, were present In only 21.4% of the DIC patients. Combinations of PI'TK >38 sec with PT >15 sec or platelet count < 1.5 Iaclmm 3 were good screening tests for DIC and detected 11 and 10 patients out of 14 with three and two false positives respectively. MJAFI 2002; 58 : 13-17

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“…Obstetrical accidents are common events leading to DIC. Amniotic fluid embolism with DIC is the most catastrophic and common of the life-threatening obstetrical accidents [1][2][3][4][5][6]. The syndrome of amniotic fluid embolism is manifest by the acute onset of respiratory failure, circulatory collapse, shock, and DIC.…”

Section: Etiologymentioning

confidence: 99%

“…This catastrophic syndrome spans all areas of medicine and presents a broad clinical spectrum that is confusing to many. DIC was called 'consumptive coagulopathy' in the early literature [6,7]; this is not a proper description as very little is consumed in DIC; most factors and plasma constituents are plasmin biodegraded. Terminology following this phrase was 'defibrination syndrome' [8,9]; however, a more suitable term would be 'defibrinogenation syndrome'.…”

Section: Introductionmentioning

confidence: 99%

Disseminated Intravascular Coagulation

Bick¹,

Arun²

1999

Pathophysiol Haemos Thromb

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Disseminated intravascular coagulation (DIC) is a complex disorder, with pathophysiology being variable and highly dependent upon the triggering event(s), host response(s) and comorbid conditions. As a result of these complicated interactions, the clinical expression and laboratory findings are varied, thereby affecting the specifics of diagnosis and therapeutic approaches. The highly complex and variable pathophysiology of DIC often results in a lack of uniformity in clinical manifestations, a lack of consensus in the specific appropriate laboratory criteria of diagnosis, and a lack of specific therapeutic modalities. Indeed, recommendations for therapy are often difficult because the morbidity and survival is more dependent on the specific cause of DIC and because the generally used specific therapeutic approaches, which include for example heparin, low-molecular-weight-heparin antithrombin concentrate and protein C concentrate, have never been subjected to objective prospective randomized trials, except antithrombin concentrates. An analysis of the complex and varied pathophysiological events in DIC provide objective guidelines and criteria for the clinical diagnosis, the laboratory diagnosis, and the definition of severity. These data compounded by an understanding of complex and varied pathophysiology can be used for objective evaluation of therapeutic responses and results. DIC is an intermediary mechanism of disease usually seen in association with well-defined clinical disorders. The pathophysiology of DIC serves as an intermediary mechanism in many disease processes, which sometimes remain organ specific. This catastrophic syndrome spans all areas of medicine and presents a broad clinical spectrum that is confusing to many. Most physicians consider DIC to be a systemic hemorrhagic syndrome; however, this is only because hemorrhage is evident and often impressive. Less commonly appreciated is the profound microvascular thrombosis and sometimes, large vessel thrombosis. The hemorrhage is often simple to contend with in patients with fulminant DIC, but it is the small- and large-vessel thrombosis, with impairment in blood flow, ischemia, and associated end-organ damage that usually leads to irreversible morbidity and mortality. In conclusion, the pathophysiological mechanisms, clinical, and laboratory manifestations of DIC are complex in part due to interrelationships within the hemostasis system. Only by clearly understanding these extraordinarily complex pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Many therapeutic decisions to be made are controversial and lack validation. Nevertheless, newer antithrombotic agents, and agents which can block, blunt or modify cytokine activity and the activity of vasoactive substances appear to be of value. The complexity and variable degree of clinical expression suggests that therapy should be individualized depending o...

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Pathophysiology, clinical manifestations and therapy of consumption-coagulopathy (“Verbrauchskoagulopathie”)

Cited by 164 publications

References 30 publications

Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model

Factor V Leiden mutation enhances fibrin formation and dissolution in vivo in a human endotoxemia model

DIAGNOSING DISSEMINATED INTRAVASCULAR COAGULATION IN ACUTE INFECTION : CAN WE DO WITHOUT FDP & D-DIMER

Disseminated Intravascular Coagulation

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