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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • DIC is an acquired coagulation dysfunction characterized by marked activation of the coagulation system that causes excessive thrombin activation, fibrin formation, and widespread intravascular fibrin deposition
  • The exaggerated activation of coagulation and subsequent deposition of microthrombi can lead to:
    • Ischemic lesions in organs and development of multiorgan failure
    • Depletion of platelets and coagulation factors (consumption coagulopathy), which may cause secondary hemorrhage
  • DIC is always secondary to a severe underlying disorder. Endotoxemia secondary to GI disorders and septicemia are the main causes of DIC in adult horses and neonatal foals, respectively

Pathophysiology!!navigator!!

  • Underlying diseases induce platelet activation and excessive thrombin formation, and may induce endothelial damage, inhibition of coagulation inhibitors, and defective fibrinolysis. These combine to produce uncontrolled fibrin deposition and consumptive coagulation
  • 2 clinical forms of DIC can be observed:
    • The MOFS form occurs when activation of coagulation is severe and fibrinolytic activity is inhibited. Widespread fibrin formation and microthrombus deposition in the microcirculation produce ischemic damage to tissues, contributing to MODS and MOFS
    • The hemorrhagic form occurs when activation of coagulation is less severe and excess fibrin formation can be arrested by the fibrinolytic system. Increased consumption of coagulation factors and platelet depletion may cause a consumptive coagulopathy and a subsequent hypocoagulable state, resulting in bleeding diatheses
  • Despite some debate there is evidence to indicate that DIC contributes to multiple organ failure

Systems Affected!!navigator!!

  • Hemic/lymphatic/immune—excessive fibrin formation and deposition occurs in blood vessels
    • Hypercoagulation may induce vessel thrombosis after endothelial damage associated with venipunctures or catheters
  • Other systems may be affected depending on the organ affected by deposition of microthrombi, and/or the sites of hemorrhage

Incidence/Prevalence!!navigator!!

  • DIC is the most frequent hemostatic disorder of the horse. It has been reported in 55% of ischemic and 36% of severe inflammatory GI disorders
  • DIC is also diagnosed in many septic newborn foals (>50%)

Signalment!!navigator!!

N/A

Signs!!navigator!!

General Comments

Clinical signs include those of the underlying disease and of DIC.

Historical Findings

Dependent upon underlying disease.

Physical Examination Findings

  • In the MOFS form of DIC, horses may demonstrate clinical signs referable to the affected organ including hypotension, dyspnea, tachypnea, oliguria, colic, cardiac arrhythmias, etc.
  • In the hemorrhagic form of DIC, horses may have hemorrhagic diatheses, with excessive bleeding after wound or minor trauma, petechiae, or spontaneous bleeding from mucous membranes (i.e. epistaxis, melena)
  • Catheter and venipuncture site thrombosis is common

Causes!!navigator!!

  • Ischemic or inflammatory GI disorders
  • Endotoxemia
  • Neonatal septicemia
  • Heat stroke
  • Less common—severe hemolysis, disseminated neoplasia, and other systemic inflammatory conditions (e.g. snake bite)

Risk Factors!!navigator!!

Any disease or treatment that severely activates platelets and/or coagulation pathways, inhibits the fibrinolytic system, or causes significant endothelial damage.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • The MOFS form of DIC requires differentiation from other causes of hypotension, renal failure, hypoxemia, etc.
  • The hemorrhagic form of DIC requires differentiation from other coagulation deficiencies (acquired or inherited)

CBC/Biochemistry/Urinalysis!!navigator!!

  • Thrombocytopenia (<100 000 platelets/µL) due to platelet consumption
  • In cases of MODS or MOFS, plasma biochemistry abnormalities may be detected depending on organ dysfunction (e.g. increase in creatinine, blood urea nitrogen, liver enzymes, etc.)

Other Laboratory Tests!!navigator!!

  • Laboratory evidence may include:
    • Consumptive coagulopathy is detected by evaluating clotting times (PT and aPTT), but this is not specific for DIC. A decrease in fibrinogen concentration is also consistent with clotting factor consumption
    • Fibrinolytic activation increases plasma d-dimer concentration. In DIC patients concentrations may be >2000 ng/mL. This test is sensitive for DIC, but has low specificity
    • FDPs have also been used to assess fibrinolysis, but are less reliable and decreasingly used
    • Coagulation inhibitor consumption may be measured through decreases in concentrations of antithrombin activity and protein C
  • No single laboratory test is sufficiently sensitive or specific, therefore a diagnosis of DIC requires a combination of laboratory findings (e.g. thrombocytopenia, prolonged clotting times, increased d-dimers, and reduced antithrombin and fibrinogen) in conjunction with appropriate clinical signs
  • In the equine veterinary literature, horses are considered to have subclinical DIC if they have abnormalities in 3 of 6 traditionally available tests: (1) platelet count, (2) PT, (3) aPTT, (4) antithrombin activity, (5) fibrinogen, and (6) either d-dimers or FDPs. Horses in subclinical DIC are at risk of developing overt clinical DIC as natural coagulation inhibitors become overwhelmed

Pathologic Findings!!navigator!!

  • Petechiae and ecchymoses may be seen on postmortem
  • Thrombosis may be observed grossly, but microthrombosis is commonly misdiagnosed on histologic examinations when using routine stains
  • Specific histochemical (PTAH) or immunohistochemical stains are required to accurately detect fibrin deposition in capillaries

Treatment ⬆ ⬇

Outline

TREATMENT

Aims!!navigator!!

  • The primary aim of treatment is to control the underlying disease causing the severe, hypercoagulable state
  • The second aim is to control the hypercoagulable state (and subsequent consumptive coagulopathy)
  • The mortality rate of DIC is low if patients are diagnosed and treated during the early stages of disease, but becomes high when multiorgan failure and/or bleeding diatheses are present. Thus, a key objective for management of DIC is to treat patients at risk of DIC in order to prevent hypercoagulation from developing
  • Supportive therapy is required to reduce microthrombi deposition and secondary organ dysfunction and/or failure

Appropriate Health Care!!navigator!!

DIC requires emergency hospitalization and intensive care management.

Nursing Care!!navigator!!

  • Fresh (or fresh frozen) plasma transfusion (12–20 mL/kg) is only required in cases with severe consumptive coagulopathy and bleeding diatheses. This treatment slows progression of DIC and may help improve metabolic derangements caused by some primary diseases
  • Low-dose heparin therapy has also been given to patients with DIC added to the transfusion bags. However, the high cost of plasma transfusions and the poor prognosis of the hemorrhagic form of DIC makes this treatment difficult and impractical in horses
  • Horses with DIC may require intensive fluid therapy to control shock, improve tissue blood supply, and reduce multiorgan failure. Crystalloid solutions (e.g. lactated Ringer's solution) are commonly used, but colloidal solutions (e.g. hetastarch) may also be indicated

Activity!!navigator!!

Limited as required for patients in intensive care.

Diet!!navigator!!

According to restrictions/prescriptions associated with the underlying disease.

Surgical Considerations!!navigator!!

Only if the underlying disorder requires surgery.

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Antithrombotics (e.g. heparin) are administered in the early stages of DIC to reduce the excessive coagulation activation. They are the most effective treatment for control of this disorder, although their administration has been considered controversial
  • LMWH (e.g. dalteparin, enoxaparin) are preferred as they do not produce many of the detrimental effects associated with unfractionated heparin, such as erythrocyte agglutination. The safest dose of LMWH is 50 IU/kg of dalteparin SC every 24 h (or 0.5 mg/kg of enoxaparin) over 3–4 days. If no LMWH is available, unfractionated heparin is recommended (40–100 IU/kg every 12 h)
  • Unfractionated heparin administration—sodium heparin (SC or IV), calcium heparin (SC)
  • The use of antiplatelet agents (e.g. aspirin) to reduce the hypercoagulable state has not been shown to be effective in horses (unlike humans or small animals)
  • Clopidogrel has been demonstrated to be an effective platelet inhibitor in healthy horses, but efficacy in horses with a hypercoagulable state is unknown. Interindividual variability in the response to clopidogrel may influence clinical efficacy

Contraindications!!navigator!!

  • Antifibrinolytic drugs (e.g. aminocaproic acid) should not be used in hemorrhagic patients, as it impairs fibrinolysis and worsens hypercoagulation, microthrombi deposition, and DIC
  • Hypertonic saline solution should not be used to control hypotension as it may cause hemodilution of coagulation factors and increase the risk of bleeding

Possible Interactions!!navigator!!

Colloidal solutions may be administered to patients with DIC to treat the hypoalbuminemia caused by the underlying disease (e.g. colitis). Colloidal administration may reduce platelet function and may prolong hemorrhage.

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Repeated physical examinations, with particular attention to evidence of MODS, MOFS, bleeding, or venous thrombosis, should be performed
  • PT, aPTT, d-dimer concentration, and platelet counts should be monitored to assess clinical progression and effectiveness of treatment
  • In cases of MODS/MOFS, biochemical parameters indicative of tissue dysfunction should be monitored

Possible Complications!!navigator!!

  • MODS
  • MOFS
  • Shock
  • Acute renal failure
  • Laminitis
  • Thrombophlebitis
  • Fatal bleeding
  • Death

Expected Course and Prognosis!!navigator!!

  • With clinical signs of DIC, prognosis is guarded to poor. High mortality rates are due to the combination of DIC and severity of the underlying disease
  • Prognosis is better if:
    • DIC is diagnosed early
    • Preventive treatment is effectively introduced

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Localized or systemic ischemic or inflammatory disorders
  • Heat stroke
  • Others; severe hemolysis, disseminated neoplasia (i.e. melanosarcoma), etc.

Synonyms!!navigator!!

Consumptive coagulopathy

Abbreviations!!navigator!!

  • aPTT = activated partial thromboplastin time
  • DIC = disseminated intravascular coagulation
  • FDP = fibrin(ogen) degradation product
  • GI = gastrointestinal tract
  • LMWH = low-molecular-weight heparin
  • MODS = multiorgan dysfunction syndrome
  • MOFS = multiorgan failure syndrome
  • PT = prothrombin time
  • PTAH = phosphotungstic acid–hematoxylin

Suggested Reading ⬆ ⬇

Cesarini C, Monreal L, Armengou L, et al. Association of admission plasma D-dimer concentration with diagnosis and outcome in horses with colic. J Vet Intern Med 2010;24(6):1490–1497.

Cotovio M, Monreal L, Navarro M, et al. Detection of fibrin deposits in tissues from horses with severe gastrointestinal disorders. J Vet Intern Med 2007;21:308–313.

Author(s) ⬆

Author: Eduard Jose-Cunilleras

Consulting Editors: David Hodgson, Harold C. McKenzie, and Jennifer L. Hodgson

Acknowledgment: The author and editors acknowledge the prior contribution of Luis Monreal.