Disseminated Intravascular Coagulation in Dogs and Cats

C. Guillermo Couto, DVM, DACVIM

Veterinary Medicine June 1999

 

Disseminated Intravascular Coagulation = DIC or consumptive coagulopathy or defibrination syndrome

*is a complex set of events that arises when there is excessive intravascular coagulation that causes multiple-organ microthrombosis and paradoxical bleeding.

*bleeding is caused by either the inactivation of or the excessive consumption of platelets and/or clotting factors because of increased fibrinolysis

*DIC may have a gradual or acute onset, but once it has started the changes in the patient's status will occur rapidly and require intense monitoring with subsequent changes in therapy as indicated.

*common in both dogs and cats

Pathogenesis

DIC (essentially an exaggeration of normal hemostatic mechanisms) may occur due to the following conditions:

Electrocution/heatstroke - produce endothelial damage, may result in sepsis-associated DIC

Viral infections - activates platelets (FIP)

Trauma, hemolysis, pancreatitis, bacterial infections, acute hepatitis, some neoplasms (hemangiosarcoma) - causes release of tissue procoagulants

Activation of the coagulation cascade due to one of the above events causes the results below which may happen simultaneously:

TRAUMA causes:

1.

Formation of primary and secondary hemostatic plugs

2.

Activation of the fibrinolytic system

 

3.

Consumption of antithrombin III, and potentially proteins C & S

4.

Fibrin formation in microcirculation

which causes:
circulation of microthrombi
platelet consumption
clot lysis
inactivation of clotting factors*
impaired platelet function*
attempt to halt intravascular coagulation
hemolytic anemia
results in:
ischemia
thrombocytopenia*
to minimize exhaustion of normal anticoagulants
schistocytosis (fragmented red blood cells)
appears as:
Primary: petechiae, ecchymoses, mucosal bleeding
Secondary: blood in body cavity
* cause spontaneous bleeding

"Enhancers" of DIC include hypoxia; acidosis; hepatic, renal, and pulmonary dysfunction; and release of myocardial depressant factor. These occur when tissue perfusion is impaired.

The mononuclear phagocytic system function is also impaired which leads to a build up of FDPs, other byproducts, and bacteria absorbed from the intestine in the blood stream which can not be cleared.

The paradox is administration of heparin (an anticoagulant) to stop the bleeding. Heparin acts with antithrombin III (must be enough available to do this) to stop intravascular coagulation and thus slows the fibrinolytic activity which then decreases its inhibitory effect of the clotting factors and platelet function.

Diseases and Conditions Associated with DIC in Dogs and Cats
Neoplasia
Infectious disorders
Inflammatory conditions
Miscellaneous

Hemangiosarcoma (D)
Hemangioma
Metastatic thyroid
carcinoma
Metastatic mammary
carcinoma
Prostatic adenocarcinoma
Lymphoma (C)
Cholangiocarcinoma

 

D=most common in dog

C=most common in cat

 

Sepsis
Bacterial endocarditis
Leptospirosis
Canine infectious
hepatitis (D)
Babesiosis
Dirofilariasis
Feline infectious
peritonitis (C)

 

 

 

 

 

Suppurative dermatitis
Suppurative bronchopneumonia
Acute hepatic necrosis
Chronic active hepatitis
Pancreatitis
Hemorrhagic gastroenteritis
Erythema multiforme

 

 

 

 

 

Shock
Heatstroke
Venomous snakebite
Cirrhosis
Aflatoxicosis
Immune-mediated hemolytic
anemia (D)
Cold agglutinin disease
Gastric dilatation-volvulus
Congestive heart failure
Valvular fibrosis
Diaphragmatic hernia
Perioperative complications
Eumycotic mycetoma
Renal amyloidosis
Pulmonary thromboembolism
Hepatic lipidosis (C)

Clinical Features
1. Chronic silent (subclinical) - Patients usually do not have spontaneous bleedings, but hemostatic system values are abnormal, compatible with DIC. This is the most common form seen in cats and in dogs with concomitant malignancy or chronic disorders.
2. Acute (fulminant) - Seen after true acute trauma or in patients that have an ongoing subclinical disease that causes an sudden decompensation. In many dogs, DIC is diagnosed secondarily to a primary problem that does not include spontaneous bleeding. Clinical signs of primary and secondary hemostatic defects and (pathologically) organ dysfunction are seen..

Diagnosis (focus here is on dogs, since cats rarely have clinical DIC)
1. Hemogram (hematocrit and blood smear evaluation) is recommended, look for signs of hemolytic anemia, hemoglobinemia (caused by intravascular hemolysis), hemoglobinuria, RBC fragmentation or schistocytes, thrombocytopenia, left shift neutrophilia, and rarely neutropenia.
2. Serum chemistry evaluation will show hyperbilirubinemia secondary to hemolysis or hepatic thrombosis, azotemia, and hyperphosphatemia (with severe renal microembolization), increased liver enzymes (due to hypoxemia or hepatic microembolization), decreased total CO2 (metabolic acidosis), and possibly panhypoproteinemia (severe bleeding).
3. Urinalysis shows hemoglobinuria, bilirubinuria, and occasional proteinuria and cylindruria. NOTE: do not obtain sample via cystocentesis.
4. Hemostatic changes include thrombocytopenia, prolonged OSPT (>25% of current control) and/or prolonged APTT, hypofibrinogenemia, positive FDPs test, decreased antithrombin III concentration, and often enhanced fibrinolysis (decreased plasminogen activity, enhanced clot lysis test)
*A patient is considered to have DIC when he/she exhibits 4 or more of the above abnormalities and has schistocytosis (author).

Treatment
Confirmed DIC or highly suspicious DIC warrants immediate treatment in both dogs and cats:
1. Proactively attempt to eliminate the initial cause (may include surgery) and begin therapy
2. Stop intravascular coagulation by the administration of heparin, aspirin, blood or blood products (provide antithrombin III)
3. Maintain parenchymal organ perfusion by initiating aggressive fluid therapy
4. Prevent secondary complications by maintaining oxygenation, evaluating acid-base status and correcting it if needed, correcting cardiac arrhythmias, and administering antibiotics.
*Author notes that most DIC dogs die of pulmonary or renal dysfunction usually denoted by intrapulmonary hemorrhages with alveolar septal microthrombi (DIC lungs), not hypovolemic shock.

Halting intravascular coagulation
Administration of heparin and blood or blood products. Heparin must have sufficient antithrombin III activity in the plasma (hence administration of fresh whole blood or fresh-frozen plasma). Heparin has not been scientifically determined to be helpful, but clinical evidence (author) show improved survival in DIC patients treated with it.
Heparin Dose Ranges:
1. Mini-dose heparin: 5 - 10 U/kg SC TID
2. Low-dose heparin: 100 - 200 U/kg SC or IV TID
3. Intermediate-dose heparin: 300 - 500 U/kg SC or IV TID
4. High-dose heparin: 750 - 1,000 U/kg SC or IV TID
Author recommends use of mini-dose heparin with blood/blood products to minimize affect on the ACT or APTT in normal dogs. (Note: 150 - 250 U/kg TID heparin is needed to prolong APTT in normal dogs). If a DIC patient on mini-dose heparin has a prolonged ACT or APTT, intravascular coagulation is progressing facilitating a treatment change.
Therapy: Initial heparin dose is added to the blood/plasma prior to transfusion and allowed to sit at room temperature for 30 minutes (heparin/antithrombin III interaction complex is thus formed and activated)
*If the patient has marked azotemia/isosthenuric urine/increased liver enzyme activity (severe microthrombosis), dyspnea, or hypoxemia use the intermediate or high-dose heparin to prolong ACT (up to 2 or 2 & 1/2 times baseline or normal).
*If overheparinization occurs give protamine sulfate slow IV infusion (1 mg/ 100 U of the last dose of heparin given) as 50% of the calculated dose one hour after heparin, and 25% given two hours after the heparin, with the remaining amount given only if clinically warranted. NOTE: acute anaphylaxis may occur with protamine sulfate injection in dogs.
*Once clinical and clinicopathologic features have improved, taper the heparin dose gradually over 3 - 4 days.
Aspirin Dosages: (used to prevent platelet activation, halting intravascular coagulation)
Dogs: 5 - 10 mg/kg PO BID
Cats: 5 - 10 mg/kg PO q third day
Author notes rare clinical benefit, monitor for GI bleeding (could be life threatening in patients with severe coagulopathy-DIC)

Maintaining parenchymal organ perfusion
Aggressive fluid therapy with crystalloids or plasma expanders (dextran) to dilute clotting and fibrinolytic factors, flush out microthrombi, and maintain precapillary and arteriole patency to increase blood flow to hypoxic areas. Note: do not overhydrate compromised renal or cardiopulmonary patients.

Preventing secondary complications
Maintain oxygen mask, cage oxygen, or nasopharyngeal catheter
Correct acidosis and cardiac arrhythmias
Prevent secondary bacterial infections
Note: avoid central IV lines - can cause catheter associated thrombosis of the anterior vena cava >>chylothorax.

Prognosis
Dogs with DIC = grave prognosis unless the initial cause is eliminated quickly and appropriate therapy is initiated as soon as possible.