Drugs & Blood Products Used to Manage Bleeding Disorders

Platelet-rich plasma is separated from freshly collected blood within 4 to 6 hours of collection, before refrigeration (39°F [4°C]; standard range for all refrigerated blood products, 33.8°F-42.8°F [1°C-6°C]; hereafter noted as 39°F [4°C]), and using a specialized centrifugation technique to produce supernatant plasma rich in platelets. Platelet-rich plasma has a short shelf life and is typically made on demand by onsite blood banks or as a special order from commercial blood banks.^11,12

Indications

• Life-threatening hemorrhage due to thrombocytopenia

• Prophylaxis prior to invasive diagnostics or surgery in patients with severe thrombocytopenia

Dosage (Dogs, Cats)

• 10 mL/kg IV transfusion over 1 to 2 hours¹¹

  • May be administered faster in a hemorrhagic crisis

  • Patients in a severe bleeding crisis may require a significantly higher dose. 

Key Points

• Product can be stored refrigerated at 39°F (4°C) for 72 hours from the time of blood collection.¹¹

Frozen platelet concentrate can be produced either by further centrifuging platelet-rich plasma to remove some of the plasma volume or by plateletpheresis; it is then preserved in dimethyl sulfoxide (ie, DMSO) solution prior to freezing.^3,11,13

Indications

• Life-threatening hemorrhage due to thrombocytopenia

• Prophylaxis prior to invasive diagnostics or surgery in patients with severe thrombocytopenia

Dosage (Dogs, Cats)

• 10 mL/kg IV transfusion over 1 to 2 hours¹¹

  • May be administered faster in a hemorrhagic crisis

  • Patients in a severe bleeding crisis may require a significantly higher dose. 

Key Points

• Product can be stored frozen at or below −0.4°F (−18°C) for 6 months from date of production and should be used immediately after thawing in a water bath at 98.6°F (37°C).¹¹

Lyophilized platelets are produced by plateletpheresis and subsequent lyophilization, allowing storage at room temperature (64.4°F-86°F [18°C-30°C]) and a longer shelf life.

Indications

• Life-threatening hemorrhage due to thrombocytopenia

• Prophylaxis prior to invasive diagnostics or surgery in patients with severe thrombocytopenia^3,7,11,13,14

Dosage (Dogs, Cats)

• 3 × 109 platelets/kg or 2 mL/kg when reconstituted according to manufacturer instructions over 15 to 20 minutes^11,14

Key Points

• Product can be stored at room temperature (64.4°F-86°F [18°C-30°C]) for 2 years from date of production and should be used within 1 hour of reconstitution.¹⁴ 

• Currently only available for dogs

Whole blood is blood collected from a donor and stored in preservative solution without further alteration or separation into component parts.

Indications

• Bleeding due to inherited and acquired coagulation disorders^3,7,11,13,14 

Dosage (Dogs, Cats)

• Initially, 1 unit/10 kg (≈15 mL/kg) IV transfusion over 1 to 4 hours for severe thrombocytopenia, clotting factor deficiency, and vitamin K antagonism^{3,5,6,11,13,15-18}

  • Additional transfusions as indicated by volume of blood loss, perfusion parameters, and hematocrit

  • May be administered more rapidly in a hemorrhagic crisis¹⁸

  • 10 mL/kg of fresh whole blood is expected to raise the platelet count by ≈10,000/µL

  • ≥20-40 mL/kg typically controls hemorrhage in patients with vitamin K antagonism and inherited coagulopathies

Key Points

• Product can be stored refrigerated at 39°F (4°C) up to 21 days from collection for platelet transfusion.¹⁸ 

  • RBCs remain viable longer, depending on the anticoagulant and cell preservatives added to the collection bag.¹⁸

• It was previously believed that only fresh whole blood (not blood stored in the refrigerator) contained active platelets, but recent evidence shows refrigerated canine whole blood retains most of its clot strength for up to 21 days.^15,16

Cryoprecipitate is rich in factor VIII, factor XIII, fibrinogen, and von Willebrand factor that is available in lyophilized or frozen forms and is produced from fresh frozen plasma in commercial and onsite blood banks.⁵

Indications

• Bleeding due to von Willebrand disease and hemophilia A⁵

Dosage (Dogs, Cats)

• 1 unit/10 kg (≈1 mL/kg) IV transfusion over 30 to 60 minutes for prophylaxis⁵

• 1 unit/10 kg (≈1 mL/kg) IV transfusion over 30 to 60 minutes, repeated continuously until bleeding stops for bleeding crisis5

  • Much larger volumes (ie, ≥10-30 mL/kg) are usually required for hemorrhagic crisis.

Key Points

• Frozen product can be stored frozen at or below −0.4°F (−18°C) for 1 year from date of production and should be used within 24 hours of thawing in a water bath at 98.6°F (37°C).¹¹

• Lyophilized product can be stored refrigerated at 39°F (4°C) for 18 months from date of production (prior to reconstitution) and should be used within 24 hours of reconstitution.¹⁹ 

• Canine product is generally available from most commercial blood banks and can be produced by onsite donor programs with the appropriate type of blood banking centrifuge.

• Feline product is usually made to order (resulting in longer delay to shipping) and only available from a few commercial blood banks; however, it can also be made by onsite donor programs with the appropriate type of blood banking centrifuge.

Cryo-poor plasma (ie, cryosupernatant) is the plasma product that remains after cryoprecipitate has been removed from a processed bag of fresh frozen plasma and contains factors II, VII, IX, X, XI, XII, and XIII, as well as fibrinogen, albumin, and globulins. Cryo-poor plasma is produced in commercial and onsite blood banks.^6,20

Indications

• Bleeding in patients with hemophilia B

• Bleeding crisis due to vitamin K antagonism^6,20

Dosage (Dogs, Cats)

• 1 unit/10 kg (≈8-10 mL/kg) IV transfusion over 1 to 4 hours for prophylaxis 

• 1 unit/10 kg (≈8-10 mL/kg) IV transfusion over 30 to 60 minutes, repeated continuously until bleeding stops for hemophilia B bleeding crisis

• 20-40 mL/kg IV transfusion over 1 to 4 hours for vitamin K antagonism

  • Larger volumes often required for patients in bleeding crisis^6,20

  • May be given faster during bleeding crisis^6,19

Key Points

• Product can be stored frozen at or below −0.4°F (−18°C) for 1 year from date of production and should be used within 4 to 6 hours of thawing in a water bath at 98.6°F (37°C) when used to replace depleted clotting factors.

• Product thawed and not used can be kept refrigerated at 39°F (4°C) and used within 2 weeks as refrigerated plasma.²¹

Fresh frozen plasma is plasma that has been processed and frozen at or below −0.4°F (−18°C) within 6 to 8 hours of blood collection.²⁰

Indications

• Bleeding due to von Willebrand disease, hemophilia A, and vitamin K antagonism^5,6

Dosage (Dogs, Cats)

• 1 unit/10 kg (≈10 mL/kg) IV transfusion over 2 hours for prophylaxis 

• 1 unit/10 kg (≈10 mL/kg) IV transfusion over 2 hours, repeated continuously until bleeding stops for bleeding crisis

  • May be given faster in severe bleeding crisis^5,21

Key Points

• Product can be stored frozen at or below −0.4°F (−18°C) for 1 year from date of production and should be used within 4 to 6 hours of thawing in a water bath at 98.6°F (37°C) for treatment of von Willebrand disease.

• Product thawed and not used can be refrozen within 24 hours for use as frozen plasma or kept refrigerated at 39°F (4°C) and used within 2 weeks as refrigerated plasma.²¹

Frozen plasma can be derived by processing and freezing plasma between 8 and 24 hours after blood collection, storing fresh frozen plasma at or below −0.4°F (−18°C) for >1 year, or thawing fresh frozen plasma and storing refrigerated at 39°F (4°C) for >24 hours before transfusion (subsequently called thawed plasma).²¹

Indications

• Bleeding due to von Willebrand disease, hemophilia A, and vitamin K antagonism^5,11

Dosage (Dogs, Cats)

• 1 unit/10 kg (≈10 mL/kg) IV transfusion over 2 hours for prophylaxis^5,6,21

• 1 unit/10 kg (≈10 mL/kg) IV transfusion over 2 hours for bleeding crisis, repeated continuously until bleeding stops

  • Larger volumes usually required^5,6,21

  • May be given faster in severe bleeding crisis^5,21

Key Points

• Product can be stored frozen at or below −0.4°F (−18°C) for 1 year from date of production and should be used within 4 to 6 hours of thawing in a water bath at 98.6°F (37°C) for treatment of von Willebrand disease.

• Some studies indicate levels of factors V and VIII decrease and possibly become subtherapeutic, depending on length of storage.^5,6,21

• Product thawed and not used can be refrozen within 24 hours for use as frozen plasma or kept refrigerated at 39°F (4°C) and used within 1 week as thawed plasma.²¹

Vitamin K supplement; antidote for vitamin K antagonism due to anticoagulant rodenticides 

Indications

• Treatment of vitamin K antagonism in coagulopathic patients and in subclinical or preclinical patients with vitamin K antagonist exposure

• Vitamin K supplement for patients with hepatic disease

Dosage (Dogs, Cats)

• 1-5 mg/kg PO, IM, or SC every 24 hours or divided and given every 12 hours

Key Points

• May take 6 to 12 hours for clinically significant amounts of active clotting factors to be produced once treatment is initiated

• Absorption from the GI tract is enhanced when administered with a meal. 

• Patients with active hemorrhage should be treated with blood products (eg, whole blood, fresh frozen plasma) to stop bleeding and treat anemia (see RBC and plasma products sections).

• Coagulopathic patients may bleed from injection sites. 

• Oral administration can be considered if the GI tract is working.

• Small-gauge needles for injection should be used if oral administration is not possible.

• Duration of treatment depends on the specific toxin and total amount ingested. 

• Toxicology reference publications, animal poison control centers, veterinary toxicologists, and product manufacturer instructions should be used to determine duration of treatment.

Desmopressin is a synthetic analogue of vasopressin.

Indications

• Bleeding due to von Willebrand disease^5,22

Dosage (Dogs)

• 1-4 µg/kg SC 30 minutes preoperatively for prophylaxis^5,22

• 4 µg/kg SC once for bleeding crisis⁵ 

Key Points

• Administration causes release, not production, of stored von Willebrand factor from the endothelium and, therefore, is generally only effective once in a 24-hour period.⁵

• Can be repeated every 24 hours for the duration of a bleeding crisis, although the efficacy of subsequent doses is unknown

• Available from most commercial human pharmacies in a nonsterile nasal spray formulation that can be administered SC 

• No information is available regarding this drug for cats with von Willebrand disease.

Epsilon aminocaproic acid is an antifibrinolytic drug used to treat hyperfibrinolysis and prevent postoperative bleeding in greyhounds. Either aminocaproic acid or tranexamic acid should be used, not both; choice typically depends on clinician preference and drug availability.

Indications^7,23-26

• Hyperfibrinolysis

• Prophylaxis for postoperative bleeding in greyhounds (and possibly other sighthounds)^7,23-26

Dosage (Dogs)

• 50-100 mg/kg IV or PO every 6 to 8 hours^23,24

Key Points

• The injectable formulation can also be given orally (in place of tablets if desired and based on availability).

• Rapid IV administration may cause bradycardia and hypotension.

• Rarely causes GI upset

• There are no published data on use of antifibrinolytic drugs in cats.

Tranexamic acid is an antifibrinolytic drug used to treat hyperfibrinolysis and prevent postoperative bleeding in greyhounds. Either aminocaproic acid or tranexamic acid should be used, not both; choice typically depends on clinician preference and drug availability.

Indications^7,25-28

• Hyperfibrinolysis

• Prophylaxis for postoperative bleeding in greyhounds (and possibly other sighthounds)^7,23-26

Dosage (Dogs)

• 10-20 mg/kg IV over 2 to 20 minutes or PO every 6 to 8 hours²⁸

• There are no reported doses for treating coagulopathy in cats.

Key Points

• Rapid bolus may cause vomiting in dogs.

• One study evaluated surgical blood loss associated with carcinoma and sarcoma mass removal in cats.²⁸ Results showed that 15 mg/kg IV administered at induction reduced surgical blood loss; it is not known how this relates to cats with coagulopathy.

Yunnan Baiyao is a Chinese herbal supplement purported to have hemostatic properties.^29-32 The active ingredients are unknown and not disclosed by the manufacturer. 

Although there is anecdotal evidence supporting use of Yunnan Baiyao, results of studies evaluating effects on coagulation parameters in dogs are inconsistent, with some showing no effect and others showing a change from baseline measurements but generally staying within the normal reference interval. This variation may be secondary to inconsistent ingredients in batches due to lack of regulations in the nutraceutical/supplement industry, use of the wrong type of test to investigate for an effect, or lack of sensitivity of available testing modalities.^29-32 In addition, the nutraceutical may not actually alter coagulation. Other limitations include significant variability in administration and patient characteristics among various trials. Clinical studies involved patients with bleeding tumors on the spleen or heart and did not require laboratory evidence of coagulopathy as inclusion criteria. Limited evidence suggests minimal harm secondary to administration of a variety of doses,^29-32 but doses that produce consistent effects have not been identified. Based on current available evidence, identification of the underlying cause of coagulopathy and targeted therapy with the evidence-based treatments, as discussed previously, seems most beneficial.