The first step in any bleeding patient is to assess for and treat shock. Bleeding results in a decrease in oxygen-carrying capacity in the blood, both due to lack of circulating volume and due to loss of red blood cells (RBCs). Animals presenting to the veterinarian with shock due to hemorrhage will show characteristics such as tachycardia, pale mucous membranes, dull mentation, and may have tachypnea and hypothermia. If blood pressure is measured, it may be low (hypotensive) secondary to hypovolemia. Resuscitation of these patients is imperative, and stabilization may need to occur before a full diagnostic workup can be pursued. If an animal is hypovolemic due to hemorrhage, resuscitation may include intravenous crystalloid or colloid fluids, as well as a blood transfusion to treat the low RBCs. Resuscitation should occur with specific endpoints or goals in mind, such as normalizing blood pressure and heart rate, and enough fluid should be given to meet, but not exceed, these endpoints.

A first step in the diagnosis of coagulopathies is the identification, based on physical examination, of the likely underlying source of the coagulopathy. Generally, the underlying cause can be identified as a defect of primary or secondary hemostasis, although some animals may have defects in both. Identifying this difference on physical examination can help guide the choice of diagnostic tests and can also inform both emergent and long-term therapy. In some patients, especially those who have been bleeding for a prolonged time, the initiating source of the bleeding may not be apparent until the patient has been stabilized.

The anamnesis (medical history) for a bleeding patient is very important. Most congenital bleeding abnormalities will present within the first 6–8 months of life, either as outright hemorrhage or as excessive bleeding during spay or neuter. A travel history is important, as well as inquiries about access to any drugs or toxins that may affect coagulation and any history of excessive bleeding.

Primary Hemostasis

Primary hemostasis is the initial formation of a blood clot, mediated by platelet interaction with subendothelial collagen exposed by damage to the vascular endothelium. In general, patients with primary hemostatic defects do not present with hypovolemic shock, but rather have more chronic, insidious blood loss. However, even small amounts of bleeding into areas like the brain or lungs can rapidly become life-threatening.

Primary hemostatic defects may be caused by an absolute decrease of platelet number (thrombocytopenia), or by platelet dysfunction (thrombocytopathia). Thrombocytopenias may be caused by immune-mediated destruction but may also be associated with systemic illness (e.g., neoplasia, rickettsial disease, disseminated intravascular coagulopathy [DIC]), bone marrow suppression, or drug reactions (e.g., trimethoprim-sulfa). Thrombocytopathias may be inherited (e.g., von Willebrand's disease, which has been reported in many breeds and is prevalent among Doberman pinschers), or may be induced by drugs (e.g., aspirin or other nonsteroidal anti-inflammatory drugs, clopidogrel) or systemic illness (e.g., uremia from renal failure).

Physical examination of animals with disorders of primary hemostasis classically includes petechiae (pin-point hemorrhage) on mucous membranes or cutaneous areas. Spontaneous bleeding from mucosal surfaces may be seen, and animals may have epistaxis or hematuria. If gastrointestinal bleeding has occurred, melena may be seen, and hyphema may be noted if bleeding into the eye has occurred.

Secondary Hemostasis

Secondary hemostasis is the activation of the soluble coagulation factors leading to the formation of a fibrin clot. Tissue factor, either on inflammatory cells, or in the vascular subendothelium, combines with factor VIIa to activate the extrinsic clotting cascade and produce a small amount of thrombin, which then activates factors XI and IX and promotes thrombin production through the intrinsic pathway. The final step of secondary hemostasis is the formation of fibrin from fibrinogen, which is the crosslinked into a fibrin mesh by factor XIII.

Animals may have congenital deficiencies of specific clotting factors, such as hemophilia, caused by decreased activity of factors VIII and IX (hemophilia A and B, respectively). Patients with severe hepatic dysfunction may also develop a coagulopathy due to lack of factor production by the liver. Systemic disease that causes consumption of coagulation factors (e.g., neoplasia, DIC) or hemorrhage can result in deficient secondary hemostasis. The most common toxin that reduces secondary hemostasis is anticoagulant (warfarin-type) rodenticides. Warfarin (Coumadin) and related compounds (e.g., brodifacoum) interfere with the function of vitamin K epoxide reductase, a necessary enzyme for the formation of factors II, VII, IX, and X (as well as anticoagulant proteins C and S).

Physical examination of animals with disorders of secondary hemostasis may show ecchymoses (bruising), or bleeding into cavities as diverse as joint capsule (hemarthrosis), pericardium (hemopericardium) or the pleural space, peritoneum, or retroperitoneum. These animals may present with hypovolemic shock due to hemorrhage and may require aggressive resuscitation. Signs of shock in these animals include pale to white mucous membranes, weak or absent femoral pulses, tachycardia, and depressed mentation.

Fibrinolysis

Although not well documented in veterinary medicine, some animals may develop hemorrhage due to excessive fibrinolysis. Following clot formation and vascular repair, the body activates plasmin to break down the clot and restore blood flow. If fibrinolysis occurs early, hemorrhage may result. Some situations, such as trauma or DIC, are associated with increased fibrinolysis. In addition, some breeds of dog may have an exaggerated fibrinolytic reaction to surgery.

Initial Diagnostics for Animals with Hemorrhage

A thorough physical exam of the animal with hemorrhage should give special attention to possible areas of hemorrhage. All mucosal surfaces should be evaluated, and a digital rectal exam must be performed to check for melena or hematochezia. Some animals may present with hyphema resulting in discomfort or blindness, or hemarthrosis causing lameness. The presence of tumors (especially on the spleen) should be assessed.

A packed cell volume (PCV) and total solids (TS) should be measured soon after the initial survey; patients with anemia due to hemorrhage will usually have a low PCV, although some patients with acute hemorrhage will have a PCV in the normal range due to splenic contraction. Any animal with blood loss (acute or chronic) will have a decreased concentration of TS. Total solids may be rapidly estimated by refractometry. A voided urinalysis may show discolored urine that may be consistent with hematuria (RBC in the urine) or pigmenturia (hemoglobin or myoglobin in the urine).

A blood smear is an essential part of initial diagnostics. A normal smear will have 10–20 platelets per high power field (100x), each platelet representing approximately 15,000 platelets per μL in circulation. Platelet dysfunction (thrombocytopathia) may be present despite adequate platelet numbers. Clumping of platelets may also occur, and the feathered edge should be evaluated for an even distribution of platelets to avoid misdiagnoses of thrombocytopenia. Platelet counts less than 20,000/μL can result in spontaneous bleeding, which may be life-threatening and are common with immune-mediated destruction of platelets (e.g., immune-mediated thrombocytopenia [ITP]), while platelet counts from 50,000–80,000/ μL may be seen with DIC, infectious disease, and neoplasia, among other diseases. Evaluation of a blood smear will also show abnormal morphology in circulating white and red blood cells (e.g., hemitropic parasites or band neutrophils).

Automated cell counters may also be used to assess the complete blood count, although these may not accurately account for platelet clumping or large platelets. It is prudent to always evaluate a blood smear when these machines are used, to verify the accuracy of the results.

It is reasonable to consider performing a clinical chemistry profile and urinalysis to evaluate for systemic disease that may contribute to hemorrhage (e.g., hepatic failure). Abdominal and thoracic radiographs or ultrasound may be indicated, depending on the results of the physical exam and screening tests. It is also reasonable in any patient presenting for hemorrhage to measure clotting times (listed below under secondary hemostasis) to rule out consumption or a mixed disorder.

If a Disorder of Primary Hemostasis Is Suspected

If a patient may have a defect of primary hemostasis, evaluation must include a platelet count. If thrombocytopenia is present, investigation should be directed towards the possible causes of decreased platelet count. If the platelet count is mildly decreased or normal, analysis of platelet function may be indicated.

Platelet function may be assessed with buccal mucosal bleeding time (BMBT). This technique uses a standardized lancet (Simplate II®, Simplate II, Organon Teknika Corp.) to make a small cut in the buccal mucosal surface in dogs, and the oral mucosal surface (near an upper canine tooth) in cats. A piece of gauze or filter paper is used to soak up the blood that drips from this incision, without disturbing the forming clot. Bleeding from the incision should stop between 3–5 minutes in dogs and cats, with formation of a gel-like plug. Thrombocytopenias (< 100,000 platelets/μL) or thrombocytopathias will prolong the BMBT. Specialized machines that evaluate platelet function include the PFA-100 (Siemens Inc.) and the platelet aggregometer. Animals with primary platelet defects and von Willebrand disease will have prolonged BMBT times as well as prolonged PFA-100 closure times.

If a Disorder of Secondary Hemostasis Is Suspected

Measurement of coagulation times can document problems in secondary hemostasis. These tests require either citrated plasma or citrated whole blood. Some point-of-care coagulation machines (manufactured in the US by Abaxis and IDEXX) simplify the measurement of clotting times and are useful in a general practice setting. The activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) evaluate the intrinsic and common coagulation pathways, while the prothrombin time (PT, OSPT) evaluates the extrinsic and common pathways. The thrombin time (TT) is a surrogate measure of fibrinogen concentration and evaluates the common pathway (specifically, the ability to convert fibrinogen to fibrin). The normal ranges for coagulation times will vary depending on the machine used.

Samples for coagulation testing should be acquired via a clean direct venipuncture and placed immediately into a plastic or siliconized glass tube containing citrate (usually 3.2%) to a volume of 1:9 citrate to blood (glass tubes activate platelets and should not be used to collect blood for coagulation testing or blood products for transfusion). It is important to ensure the correct 1:9 ratio, because test results may be altered if the volume is incorrect.

Prolongation of clotting times usually occurs when factor activity is less than 30% of normal, and analysis of the PT/aPTT profile may give clues towards the cause of hemorrhage. A patient with a defect in the intrinsic pathway (e.g., hemophilia) will have a normal PT with a prolonged aPTT. Dogs with low concentrations of factor VII will have normal aPTT, with prolonged PT. Depending on the results of coagulation testing, further investigations may involve specific analysis to determine the activities of individual coagulation factors.

Disorders of Fibrinolysis

Fibrinolysis is difficult to measure without advanced equipment. Measurement of plasma d-dimer concentration (a marker of clot breakdown, a more specific fibrin(ogen) degradation products [FDP]) may increase in patients with fibrinolysis, and elevated d-dimers in the presence of a secondary coagulopathy or thrombocytopenia may indicate a diagnosis of DIC. Other methods, such as thromboelastography, may be useful for interrogating fibrinolytic potential, but this has not been completely assessed in veterinary medicine.

N = Normal; P = Prolonged; E = Ecchymoses; POE = Possible ecchymoses; PE = Petechiae; D = Decreased