Clinical Review

Disseminated Intravascular Coagulation

2017 September;12(5):16-28

References

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2. De Jonge E, Levi M, Stoutenbeek CP, Van Deventer SJH. Current drug treatment strategies for disseminated intravascular coagulation. Drugs 1998;55:767–77.

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4. Levi M, ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999;341:586–92.

5. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers 2016;2:16037.

6. Kolev K, Longstaff C. Bleeding related to disturbed fibrinolysis. Br J Haematol 2016;175:12–23.

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8. Toh CH, Alhamdi Y, Abrams ST. Current pathological and laboratory considerations in the diagnosis of disseminated intravascular coagulation. Ann Lab Med 2016;36:505–12.

9. Yu M, Nardella A, Pechet L. Screening tests of disseminated intravascular coagulation: guidelines for rapid and specific laboratory diagnosis. Crit Care Med 2000;28:1777–80.

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12. Levi M. Disseminated intravascular coagulation. Crit Care Med 2007;35:2191–5.

13. Nogami K. The utility of thromboelastography in inherited and acquired bleeding disorders. Br J Haematol 2016;174:503–14.

14. Gonzalez E, Moore EE, Moore HB. Management of trauma-induced coagulopathy with thrombelastography. Crit Care Clin 2017;33:119–34.

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17. Murrin RJ, Murray JA. Thrombotic thrombocytopenic purpura: aetiology, pathophysiology and treatment. Blood Rev 2006;20:51–60.

18. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood 2017;129:2836–46.

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Amniotic fluid embolism is sudden, with the vascular collapse of the woman soon after delivery. Due to the presence of procoagulant rich fluid in the circulatory system, there is often overwhelming DIC. Therapy is directed at both supporting blood volume and correcting hemostatic defects.

HELLP

The acronym HELLP (hemolysis, elevated liver tests, low platelets) describes a variant of preeclampsia.⁹⁰ Classically, HELLP syndrome occurs after 28 weeks of gestation in a patient with preeclampsia, but can occur as early as 22 weeks in patients with antiphospholipid antibody syndrome.^91–93 The preeclampsia need not be severe. The first sign of HELLP is a decrease in the platelet count followed by abnormal liver function tests. Signs of hemolysis are present with abundant schistocytes on the smear and a high lactate dehydrogenase level. HELLP can progress to liver failure, and deaths are also reported due to hepatic rupture. Unlike TTP, fetal involvement is present in the HELLP syndrome, with fetal thrombocytopenia reported in 30% of cases. In severe cases, elevated D-dimers consistent with DIC are also found. Delivery of the child will most often result in cessation of the HELLP syndrome, but refractory cases will require dexamethasone and plasma exchange.⁹⁴ Patients should be closely observed for 1 to 2 days after delivery as the hematologic picture can transiently worsen before improving.⁹⁵

Acute Fatty Liver of Pregnancy

Fatty liver of pregnancy also occurs late in pregnancy and is only associated with preeclampsia in 50% of cases.^96,97 Patients first present with nonspecific symptoms of nausea and vomiting but can progress to fulminant liver failure. Patients develop thrombocytopenia early in the course, but in the later stages can develop DIC and very low fibrinogen levels. Mortality rates without therapy can be as high as 90%. Low blood glucose and high ammonia levels can help distinguish fatty liver from other pregnancy complications.⁹⁸ Treatment consists of prompt delivery of the child and aggressive blood product support.

Retained Dead Fetus Syndrome

Becoming rarer in modern practices, the presence of a dead fetus for many weeks (usually ≥ 5) can result in a chronic DIC state with fibrinogen depletion and coagulopathy. In some women, this is worsened at delivery. In a stable patient, a short trial of heparin prior to planning delivery can control the DIC to allow the coagulopathy to stabilize.

DRUG-INDUCED HEMOLYTIC-DIC SYNDROMES

A severe variant of the drug-induced immune complex hemolysis associated with DIC has been recognized. Rare patients who receive certain second- and third-generation cephalosporins (especially cefotetan and ceftriaxone) have developed this syndrome.^99–104 The clinical syndrome starts 7 to 10 days after the drug is administered. Often the patient has only received the antibiotic for surgical prophylaxis. The patient will develop severe Coombs’-positive hemolysis with hypotension and DIC. The patients are often believed to have sepsis and in the management of the supposed sepsis often are re-exposed to the cephalosporin, resulting in worsening of the clinical picture. The outcome is often fatal due to massive hemolysis and thrombosis.^{101,105–107}

Quinine is associated with a unique syndrome of drug-induced DIC.^108–111 Approximately 24 to 96 hours after quinine exposure, the patient becomes acutely ill with nausea and vomiting. The patient then develops a microangiopathic hemolytic anemia, DIC, and renal failure. Some patients, besides having antiplatelet antibodies, also have antibodies binding to red cells and neutrophils, which may lead to the more severe syndrome. Despite therapy, patients with quinine-induced TTP have a high incidence of chronic renal failure.

Treatment of the drug-induced hemolytic-DIC syndrome is anecdotal. Patients have responded to aggressive therapy, including plasma exchange, dialysis, and prednisone. Early recognition of the hemolytic anemia and the suspicion it is drug related is important for early diagnosis so that the incriminated drug can be discontinued.

CANCER

Cancers, primarily adenocarcinomas, can result in DIC. The classic Trousseau syndrome referred to the association of migratory superficial thrombophlebitis with cancer¹¹² but now refers to cancer associated with thrombotic DIC.^113,114 Highly vascular tumor cells are known to express tissue factor.^114,115 In addition, some tumor cells can express a direct activator of factor X (“cancer procoagulant”). Unlike many DIC states, cancer presents with thrombosis instead of bleeding. This may be due to the inflammatory state which accompanies cancer, or it may be a unique part of the chronic nature of cancer DIC biology that allows time for the body to compensate for loss of coagulation factors. In some patients, thrombosis is the first sign of an underlying cancer, sometimes predating the cancer diagnosis by months.¹¹⁵ Rarely, the DIC can result in nonthrombotic endocarditis with micro-emboli leading to widespread small-vessel thrombosis.¹¹³

References

1. Carey MJ, Rodgers GM. Disseminated intravascular coagulation: clinical and laboratory aspects. Am J Hematol 1998;59:65–73.

2. De Jonge E, Levi M, Stoutenbeek CP, Van Deventer SJH. Current drug treatment strategies for disseminated intravascular coagulation. Drugs 1998;55:767–77.

3. Baker WF Jr. Clinical aspects of disseminated intravascular coagulation: a clinician’s point of view. Sem Thrombosis Hemostasis 1989;15:1–57.

4. Levi M, ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999;341:586–92.

5. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers 2016;2:16037.

6. Kolev K, Longstaff C. Bleeding related to disturbed fibrinolysis. Br J Haematol 2016;175:12–23.

7. Sharma S, Mayberry JC, DeLoughery TG, Mullins RJ. Fatal cerebroembolism from nonbacterial thrombotic endocarditis in a trauma patient: case report and review. Mil Med 2000;165:83–5.

8. Toh CH, Alhamdi Y, Abrams ST. Current pathological and laboratory considerations in the diagnosis of disseminated intravascular coagulation. Ann Lab Med 2016;36:505–12.

9. Yu M, Nardella A, Pechet L. Screening tests of disseminated intravascular coagulation: guidelines for rapid and specific laboratory diagnosis. Crit Care Med 2000;28:1777–80.

10. Mant MJ, King EG. Severe, acute disseminated intravascular coagulation. A reappraisal of its pathophysiology, clinical significance, and therapy based on 47 patients. Am J Med 1979;67:557–63.

11. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol 2009;145:24–33.

12. Levi M. Disseminated intravascular coagulation. Crit Care Med 2007;35:2191–5.

13. Nogami K. The utility of thromboelastography in inherited and acquired bleeding disorders. Br J Haematol 2016;174:503–14.

14. Gonzalez E, Moore EE, Moore HB. Management of trauma-induced coagulopathy with thrombelastography. Crit Care Clin 2017;33:119–34.

15. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006;354:1927–35.

16. George JN. How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Blood 2000;96:1223–9.

17. Murrin RJ, Murray JA. Thrombotic thrombocytopenic purpura: aetiology, pathophysiology and treatment. Blood Rev 2006;20:51–60.

18. Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood 2017;129:2836–46.

19. Patton JF, Manning KR, Case D, Owen J. Serum lactate dehydrogenase and platelet count predict survival in thrombotic thrombocytopenic purpura. Am J Hematol 1994;47:94–9.

20. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991;325:393–7.

21. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpurahemolytic uremic syndrome—clinical experience in 108 patients. N Engl J Med 1991;325:398–403.

22. Kaplan BS, Trachtman H. Improve survival with plasma exchange thrombotic thrombopenic purpura-hemolytic uremic syndrome. Am J Med 2001;110:156–7.

23. Kremer Hovinga JA, Coppo P, Lammle B, et al. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers 2017;3:17020.

24. Asherson RA. The catastrophic antiphospholipid syndrome [editorial]. J Rheumatol 1992;19:508–12.

25. Asherson RA, Piette JC. The catastrophic antiphospholipid syndrome 1996: acute multi-organ failure associated with antiphospholipid antibodies: a review of 31 patients. Lupus 1996;5:414–7.

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Disseminated Intravascular Coagulation

References

DRUG-INDUCED HEMOLYTIC-DIC SYNDROMES

CANCER

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