Internal Medicine 1. Treatment of Bleeding Disorders
World Small Animal Veterinary Association World Congress Proceedings, 2003
Urs Giger, PD, Dr. med. vet., MS, FVH, DACVIM, DECVIM
University of Pennsylvania
Philadelphia, PA, USA

Hemostatic disorders can be conveniently classified into vasculopathies, thrombocytopenias, thrombopathias, von Willebrand disease (vWD), and coagulopathies realizing that some disease processes cause combined hemostatic defects (e.g., disseminated intravascular coagulopathy [DIC]). A high suspicion of a hemostatic dysfunction based upon signalment, history, clinical signs, and laboratory tests, as well as definitive identification of the specific hemorrhage defect is important in order to institute promptly the most effective and safe treatment. Whereas the diagnostic approach to the bleeding patient was discussed in the previous presentation, this lecture will cover the treatment modalities for hemorrhage focusing on transfusion medicine.

Depending on the severity of the hemorrhage conservative prevention of further hemorrhage to intensive care and transfusion support may have to be instituted. There are several general therapeutic principles to consider:

 Provide local hemostasis with wound pressure, ligations, and topical agents.

 Rehydrate the patient in case of rapid blood and other fluid losses with electrolytes; avoid plasma expanders as they can induce a bleeding tendency.

 Collect diagnostic blood samples prior to treatment as blood components and drugs can affect results.

 Transfuse packed red blood cells as needed for the correction of severe anemia.

 Administer other blood components to replenish deficient or consumed coagulation factors and rarely platelets.

 Remove triggering agents such as toxins in a household and infectious agents with antimicrobial therapy.

 Treat underlying disease whenever possible, including vitamin K supplementation, immunosuppression, and other specific therapy.

 Monitor the patient's bleeding tendency and overall well-being, prevent reexposure to toxins, delay any harmful surgical interventions, and avoid exposure to drugs that impair hemostasis (e.g., aspirin, acepromazine).

Transfusion therapy

Only blood type compatible blood should be administered. Thus, patient and blood donors should be typed with simple in practice or laboratory methods, and previously transfused animals also need to be crossmatched to assure compatibility and prevent transfusion reactions. As canine blood donors should not have received any blood products previously their plasma should not contain any alloantibodies. However, cats do have naturally occurring alloantibodies and a particularly plasma from any type B cats contain very strong anti-A antibodies. Thus plasma transfusions should also be blood type matched.

Indication for blood component therapy

Disease

FWB

SWB

PRBCs

PRP

FFP

CRYO

Anemia

x

x

?

Thrombocytopenia/ Thrombocytopathia

x

?

Coagulopathies Acquired & inherited

x

?

Von Willebrand D. & Hemophilia A

x

?

Legend: ? = best component, x = other options, FWB = fresh whole blood, SWB = stored whole blood, PRBCs = packed red blood cells, PRP = platelet-rich plasma, FFP = fresh frozen plasma, CRYO = cryoprecipitate

For routine transfusion, it is not necessary to warm blood after removal from the refrigerator. Care should be taken to not overheat the blood products while thawing them (<37C). Blood components that have been prewarmed cannot be refrozen/refrigerated. Blood bags are connected to blood infusion sets that have an in-line microfilter. A long (85 cm) blood infusion set with a dripping chamber and a short infusion set (30 cm) for small dogs and cats to connect with syringes are available. Use a latex-free infusion set for platelet administration to avoid platelet aggregation.

Microfilters with 170µm pores are commonly used to remove clots and larger red cell and platelet aggregates. Finer filters with 40µm pores will remove most platelets and microaggregates.

Blood components are best administered intravenously. Ideally, an indwelling catheter (16-22 gauge depending on size of animal) is placed into the cephalic or saphenous vein on extremities may be used. In case an intravenous access cannot be obtained, red blood cells and plasma may be administered by intramedullary (or intraosseous) infusion at the trochanteric fossa (or other site). Avoid concurrent administration of drugs or fluids other than physiologic saline through the same catheter in order to prevent lysis of erythrocytes and blood coagulation.

Rate of transfusion depends on the hydration status, degree of anemia, and general health condition of an animal. Initial rate is slow, starting with 1-3 ml over the first 5 minutes to observe for any transfusion reactions, even with blood typed and/or crossmatched transfusions. This is followed by a rate of about 10-20 ml/kg/hr. In animals with cardiac failure, do not exceed 4 ml/kg/hr. Transfusion of a single bag should be completed within 4 hours.

The transfusion trigger varies widely depending on the rapidity of anemia onset and degree of the anemia as well as severity of clinical signs; there is no specific PCV at which to transfuse, but at a PCV of <15-20% oxygenation of tissues becomes drastically reduced. Volume of blood component to be administered depends on the degree of anemia and the size of the animal.

Volume (ml) of whole blood = 2 x PCV rise desired (%) x body weight (kg),

or in other words,

Administration of 2 ml whole blood/kg body weight raises the PCV by 1%.

PCV rise desired is the aim for PCV after transfusion minus the recipient's actual PCV; this formula assumes that the PCV of the blood bag is >40%. Monitor response to transfusion by obtaining PCV/TP readings prior to, immediately, and 6 and 24 hours posttransfusion, and consider continued blood loss and/or hemolysis.

In thrombocytopenia or thrombopathia, one unit of PC, PRP or FWB will increase the platelet count by 10,000/µL in a recipient weighing 30 kg. In animals with serious or life-threatening bleeding, the platelet count should be increased to above 40,000/µL. Platelet counts are monitored prior, 1 hour, and 24 hours after platelet transfusion.

In coagulopathies and von Willebrand's disease, FFP at 6-10 ml/kg is an initial dose to stop bleeding or avoid excessive bleeding during surgery. In some cases, larger volumes and repeated administration of FFP may be needed to control bleeding. Cryoprecipitate at a dose of 1 CRYO unit/10 kg or 2-4 ml/kg body weight twice daily is ideal to treat hemophilia A and von Willebrand's disease. Plasma support should be provided for an additional 1-3 days after the bleeding has been controlled to allow for healing and prevent rebleeding.

Beside the above listed general principles and described transfusion support in controlling hemorrhagic diatheses, there are several specific therapeutic interventions for particular bleeding disorders.

Immune-meditated thrombocytopenia

Platelets in the form of platelet rich plasma, platelet concentrate, or fresh whole blood, are only transfused when the patient has severe uncontrolled or life-threatening bleeding. In fact transfused platelets given to IMT patients have a very short survival of a few minutes to hours and thus do not generally increase the blood platelet count despite providing transiently improved hemostasis.

Beside treating the underlying disease, such as ehrlichiosis, babesiosis, and drug allergy, immunosuppressive agents are used to impair the macrophage system and production of platelet antibodies. Glucocorticoids are the first choice either in the form of prednisone at 1-2 mg/kg or dexamethasone at 0.2-0.3 mg/kg BID; the initial dose is slowly tapered after the recognition of a response by no more than one third the dose every 2 weeks. Vincristine at 0.02 mg/kg strictly IV once may accelerate the platelet count recovery by impairing the macrophage system, stimulating platelet release from the megakaryocytes and platelet production. Other immunosuppressive agents such as cyclosporine, azathioprine, and intravenous immunoglobulin may also be considered, but their efficacy and safety have not been documented. Finally, splenectomy is highly effective in corticosteroid refractory IMT in human patients, but has not been adequately evaluated in dogs.

Von Willebrand disease (vWD)

Cryoprecipitate, a product rich in vWF, is the blood component of choice. The dose is approximately 2-4 ml/kg or about 3-4 units of cryoprecipitate per Doberman pinscher. The cryoprecipitate or FFP transfusion may have to be repeated every 8-12 hours depending on the control of hemorrhage.

In cases of mild hemorrhage or in order to prevent excessive bleeding during minor surgeries, desmopressin at a dose of 1 µg/kg once subcutaneously may provide adequate hemostasis for a few hours. Desmopressin may improve vascular integrity as the observe increase in plasma vWF following desmopressin injection is very minimal. The effect of cryoprecipitate, FFP, and desmopressin can be monitored with the buccal mucosal bleeding time one hour after the injection.

Vitamin K antagonism (rodenticide poisoning) & deficiency

Only if the rodenticide has just been ingested should emesis be induced. When critically bleeding, vitamin K-dependent coagulation factors can be replaced with fresh frozen plasma at 10 ml/kg q 8-12 hours or with 20 ml/kg fresh whole blood, if also anemic. Vitamin K1 at an initial dose of 3-5 mg/kg per os or subcutaneously at several spots is followed by 0.5-4 mg/kg per os once daily depending on PT or PTT/ACT response. The dose and duration of treatment depends on the type and amount of the ingested rodenticide. In cases of malabsorption or biliary obstruction low parenteral doses of vitamin K are effective.

Disseminated intravascular coagulation (DIC)

Without being able to remove the trigger and treat the underlying disease (infection, cancer, IMHA, heat stroke), any therapeutic intervention seems futile. Administration of electrolyte fluids to maintain tissue perfusion and attempts to correct acidosis and hyper-/hypothermia are considered important supportive measures. However, the approaches to stop intravascular coagulation and supplement coagulation factors are highly controversial. No controlled studies in human patients and animals have documented their benefit. Heparin at a dose of 50-250 IU/kg either every 4 hours or by constant infusion have been recommended; the goal has been a 1-2 fold prolongation of the PT time above normal, but direct serum drug concentration measurements may also be helpful. Low molecular weight heparin has also been used, but cannot be monitored by the routine PTT. Other anti-thrombotic agents are also being investigated. Despite the assessment of various therapeutic strategies none have been documented to be effective in clinical practice in animals with DIC.

Speaker Information
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Urs Giger, PD, Dr. med. vet., MS, FVH, DACVIM, DECVIM
University of Pennsylvania
Philadelphia, PA, USA


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