Normal hemostasis requires each of the following components to function appropriately (Please review the role each component plays in hemostasis).

• Blood vessels
• Platelets
• Coagulation cascade
• Fibrinolytic system

When clinically (history and physical exam) evaluating patients with abnormal hemostasis consider the following:

Signalment - Is the patient more likely to have a congenital or an acquired defect? Congenital abnormalities usually manifest early in life.

History - The owners complaints about an animal with a coagulation disorder are varied. Clinical signs may reflect the location of bleeding and can include: Pale mucous membranes due to anemia or hypovolemia or both. Generalized weakness may be due to hypoxia either from anemia or hypovolemia or both. Dyspnea (difficult breathing) or tachypnea (rapid breathing) may reflect bleeding into lung or pleural space.. Tachypnea may also reflect reduced 0₂ carrying capacity. The owners may notice bruising, hematuria or blood in the feces. Bleeding into joints can cause lameness or joint swelling. Bleeding into CNS can cause neurological signs such as depression or seizures

Questions to ask the owner

Was the bleeding episode spontaneous or induced by trauma?

Is the bleeding from one or multiple sites?

Did the bleeding cease, then resume?

Have there been past episodes of bleeding? ...if yes...

• Age of onset of bleeding?
• Frequency of bleeding episodes?
• Excessive bleeding during "normal" events such as tail docking, teething, estrus?

Is there a history of related animals with abnormal bleeding? ... if yes...

• Number in litter affected?
• Sex distribution of affected animals?

Ask questions about drug or chemical exposure. Rodenticide exposure should always be considered in free roaming animals

Ask what drugs may be available to the animal or any drug treatment, for example is the animal being treated with estrogens for urinary incontinence?...Is a person in the household receiving coumarin type products as a blood "thinner"?

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Physical examination

Is the bleeding from one or multiple sites? Coagulation disorders are more likely to result in bleeding from multiple sites. Single site bleeding may be due to local disease at the site and not due to a coagulation disorder.

Is the bleeding superficial or deep?

Superficial bleeding = petechiae/ecchymosis, bleeding on mucosal surfaces including gi (melena) and urinary tract (hematuria) and epistaxis = nasal bleeding	Either superficial or deep = intraoccular bleeding	Deep bleeding into soft tissues (hematomas),   joints  (hemarthroses) or body cavities
most consistent with a vascular abnormality or reduced platelet numbers or abnormal platelet function (thrombocytopathia)	reduced platelet numbers or function  or decreased coagulation factors	Due to reduced coagualtion factors

Physical examination (continued)

If splenomegaly or hepatomegaly are present, immune mediated diseases should be considered.

Evidence of organ failure/involvement, as discussed in the history section, may be observed upon physical examination. For example, neurologic deficits may indicate bleeding into the CNS.

A rectal examination should be performed to evaluate for bleeding into the gastrointestinal tract.

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Laboratory evaluation: If you do not remember them, please review the following tests of the coagulation system. Be able to interpret abnormalities in all of the following tests. What component(s) of the coagulation system influence the results of each test?

• Activated partial thromboplastin time (APTT, PTT)
• Activated clotting time (ACT)
• One stage prothrombin time (OSPT) (PT)
• Fibrinogen
• Fibrinogen degradation products (FDPs)
• Platelet estimate: 8-10 platelets per oil immersion field (100 X objective)
• Mucosal bleeding time
• Clot retraction

Laboratory tests may also disclose evidence of concurrent organ dysfunction

Inherited diseases of hemostasis

Vascular disease such as Ehlers-Danlos syndrome are rare. Platelet function defects are called thrombocytopathia. The most common inherited thrombocytopathia is von Willibrands disease. Clotting factor deficiencies occur uncommonly. Consult a medicine textbook for a list of reported factor deficiencies.

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Acquired diseases of hemostasis

Vascular disorders can result in mild superficial bleeding and include: Animals with the following diseases may bruise more easily than a normal animal.

• Systemic lupus erythematosus (SLE)
• Cushings disease (hyperadrenocorticism)
• Diabetes mellitus

Reduced platelet numbers is called thrombocytopenia. Make sure that thrombocytopenia is repeatable. A small clot in the blood sample will tie up platelets and give the appearance of reduced numbers. This is often called "lab error" but the real error is in the collection, not in the laboratory.

Reduced numbers of platelets can be due to:

• Myelophthisic diseases
• Drug induced marrow hypoplasia (estrogen)
• Ehrlichia canis or FeLV
• Increased destruction by  immune mediated mechanisms
• Consumption in  DIC
• Sequestration in an enlarged spleen

Thrombocytopathia is normal number but decreased function of platelets. Thrombocytopathia is usually acquired:

• Uremia
• Dysproteinemia - e.g., tumor such as multiple myeloma
• Drugs - aspirin - interferes with platelet function for life of the platelet

Clotting factor deficiencies: The two most common acquired causes of factor deficiencies are antagonism of Vitamin K by rodenticides and disseminated intravascular coagulation. Severe hepatic dysfunction is a less common cause of clotting factor deficiencies

Vitamin K is necessary for hepatic activation of Factors II, VII, IX, X . Vitamin K is derived from the diet and is synthesized by bacteria in gut. Vitamin K uptake can be altered in fat malabsorption states as fat soluble vitamins are absorbed complexed with fats, or due to antibiotic alteration of GI flora. The former conditions are rare causes of reduced levels of vitamin K. Antagonism of vitamin K by rodenticides is by far, the most common cause of vitamin K associated hemostatic disorders.

There are several types of warfarin-like rodenticides on the market with different durations of activity. Signs of bleeding are seen within 3 days of warfarin ingestion. Deep bleeding is most common. Animals may display general manifestations of blood loss including hypovolemia and/or organ dysfunction from hemorrhage (e.g., pulmonary bleeding leading to respiratory distress)

A history of potential exposure (eg: free roaming animal) should raise suspicion of the possibility of rodenticide ingestion. The PT is prolonged first if diagnosed early; later both PT - PTT are prolonged.

Treatment of warfarin-like rodenticide exposure

Correct the hypovolemia with isotonic fluids and/or Fresh whole blood or Fresh plasma or Fresh frozen plasma. Administer Vitamin K. Use aquamephyton (K1) parenteral then oral. Do not use Menadione - vitamin K3. Treat for 5-7 days or longer as some rodenticides have longer durations of effect.

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DIC: disseminated intravascular coagulation

"dead in cage"

"death is coming"

DIC is defined as a concurrent activation of the coagulation and fibrinolytic systems. DIC may lead to consumption of coagulation factors, fibrinogen and platelets and subsequent bleeding, or if clot formation exceeds clot lysis, then fibrin deposition in microvasculature can result in ischemia and organ failure. DIC can be dynamic and progress from clot formation to bleeding. DIC can be caused by any disorder that causes vascular stasis or endothelial injury including generalized infection, neoplasia, severe tissue damage, and shock. There are two forms of DIC; low-grade chronic or acute fulminating. Chronic DIC is usually associated with neoplasia and patients tend to be hypercoagulable which may lead to thrombus formation. The most common locations for thrombus formation are the kidney and lung. Acute DIC is more often associated with a hypo-coagulable state (bleeding).

The following are consistent with DIC but do not all have to be present to make a diagnosis of DIC

• Thrombocytopenia
• Prolonged PT, PTT
• Hypofibrinogenemia
• fragmentation of RBC (schistocytes)
• Increased fibrin degradation products
• Reduced antithrombin III (not routinely measured by most labs)

Chronic DIC most often causes:

• mild thrombocytopenia
• hyperfibringenemia
• Increased fibrin degradation products

Treatment of DIC Treatment must be closely monitored. Many aspects of treatment for DIC are controversial

• Remove inciting cause
• Fluid therapy to maintain vascular volume and tissue perfusion
• Stop excess clotting using heparin. Avoid heparin if animal is actively bleeding or if surgery is planned (may use mini dose)

mini dose heparin: 5-10 u/kg SC every 8 hours- tests of coagulation should not be affected by this dose of heparin

low dose: 100-200 u/kg SC q8h This dose may prolong ACT or PTT

intermediate dose: 300-500 u/kg SC q 8h

high dose: 750-1000u/kg q 8h

When using any dose but the mini dose, ACT or PTT should be monitored with the goal of prolonging 2 to 2.5 times baseline

• Fresh whole blood, or fresh or fresh frozen plasma to provide coagulation factors and antithrombin III may be given in conjunction with heparin.

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General management and treatment of patients with coagulation disorders

• Individual housing to prevent injury
• Soft foods to reduce oral trauma
• Avoid elective surgery if possible
• Avoid IM injections

Transfusion therapy: Remember that coagulation factors and platelets are labile. When collecting blood, avoid contact with glass if the blood is to be used to deliver platelets and coagulation factors

Hypercoagulable states

Thrombocytosis may occur as a myeloproliferative disorder but is extremely rare

Glomerulonephropathy/amyloid result in the loss of small anticoagulant proteins like antithrombin III predisposing to hypercoagulability.

Cushings, may be associated with vascular fragility and exposure of subendothelial collagen predisposing to clot formation. The most common site of thrombosis is the main pulmonary artery resulting in acute respiratory distress.

Autoimmune hemolytic anemia may be associated with a hypercoagulable state. The mechanism is not understood. Patients that are icteric appear to be at greater risk.

DIC can be associated with either a hypo or hyper coagulable state.

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This page was last edited on December 15, 2003 by CRD
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