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| February 2006 |
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| COMMON QUESTIONS ON BLEEDING DISORDERS |
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| Can the Standard Coagulation Profile Diagnose Hemophilia? |
No, although finding a prolonged APTT with normal platelet count, PT, fibrinogen and d-dimer in
a young male animal with significant bleeding would be suggestive of hemophilia. Fibrinogen may be increased as it
is an acute phase reacting protein, and levels go up during bleeding and other times of stress. [Note: This
also can shorten the APTT result to within the upper end of reference range, thereby masking the diagnosis.] If the
patient is actively bleeding when tested, d-dimer will usually be elevated. Definitive diagnosis requires specific
coagulation factor measurement for factor VIII:C (hemophilia A) and factor IX:C (hemophilia B). |
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| Can the Standard Coagulation Profile Distinguish Rodenticide Toxicosis from DIC?
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Sometimes. The platelet count is usually normal or only slightly lowered in rodenticide exposure cases, in
comparison to moderately or very low in disseminated intravascular coagulation (DIC). In severe cases of DIC, the fibrinogen
will be moderately to severely reduced, whereas it should be normal or nearly normal in the typical rodenticide case. [Note:
While the definitive finding in DIC is stated to be high or very high d-dimer concentration, when fibrinogen is < 50 mg/dL, it
provides insufficient substrate from which to form significant amounts of d-dimer.]. Finally, a history of rodenticide or
potential rodenticide exposure, or of an underlying disease process that could predispose to DIC, is a critical determinant in
confirming the diagnosis. When in doubt, draw samples for coagulation profile and treat with vitamin K and blood products, if
indicated. |
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| Can the Standard Coagulation Profile Diagnose von Willebrand Disease (vWD)? |
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No, because most cases of vWD in animals exhibit normal platelet counts, PT, APTT, fibrinogen and d-dimer, although
the latter test may be elevated somewhat if the patient is actively bleeding at the time. Definitive diagnosis requires
assaying for von Willebrand factor antigen (vWF:Ag). This molecule is synthesized and released from endothelial cells,
and is an acute phase reacting protein so that levels can go up during bleeding and other times of stress.
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| Does Finding Low vWF:Ag Distinguish Carriers of vWD from vWD Affected Animals? |
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No, although most animals that bleed excessively due to vWD have vWF:Ag levels below 35%. Asymptomatic carriers of vWD
occasionally can have very low vWF:Ag, and animals affected with vWD occasionally can have vWF:Ag levels as high as 50%.
DNA marker testing for vWD is available for several breeds, but only the Type 3 autosomal recessive vWD of Scottish Terriers
has been validated in the scientific literature. A new collagen binding assay to assess functional vWf, available as a clinical
research tool at Cornell University, shows promise in distinguishing vWD carrier from affected animals.
When vWF:Ag is low, the definitive way to distinguish vWD carrier from affected animals is the bleeding time and clinical
history of excessive bleeding.
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| Does Finding Normal Platelet Count Rule Out Platelet-Associated Bleeding? |
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No, because platelet function is not assessed by measuring the number of platelets. As heritable platelet dysfunction exists in
animals (thrombopathia, thrombasthenia), and a variety of disease states and drugs are known to affect platelet function, the definitive
diagnosis in the presence of a normal coagulation profile and vWF:Ag would be prolongation of the bleeding time along with mucosal
surface bleeding, eccymoses, and excessive bleeding with surgical procedures.
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| Does Finding Low Platelet Count Confirm Platelet-Associated Bleeding? |
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No, although thrombocytopenia accompanied by the classical signs of petechial or ecchymotic hemorrhages or mucosal surface
bleeding would be highly suspect. In certain breeds, notably the Cavalier King Charles Spaniel and its ancestor, the English
Toy Spaniel, significantly low platelet counts (even as low as 20,000/µL) can be seen. These animals typically do not
exhibit a bleeding tendency.
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| Is Whole Blood the Preferred Treatment for Bleeding Disorders? |
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No, although cross-match compatible CPD or ACD anticoagulated whole blood may be used in any emergency situation.
The safest blood product is one that is blood-type specific and screened free of transfusion-transmitted infectious
diseases. If the cause of bleeding is known, and the patientŐs hematocrit is above 15% (20% if bleeding is acute),
fresh-frozen plasma or plasma derivatives should suffice. For patients in need of red blood cells, blood-type compatible
packed red blood cells also are given, either in sequence or simultaneously in a different vein.
In cases of hemophilia A, cryoprecipitate, a plasma concentrate derivative, is the treatment of choice given two
to three times daily until bleeding stops.
In cases of vWD, fresh-frozen plasma prepared from donors with high (> 80%) vWF:Ag given once or twice daily,
as needed, will control most bleeding episodes. For elective surgical procedures in animals with vWD, assess their current
risk to bleed excessively with a bleeding time. [Note: The transection bleeding time from cutting into the quick of a
toe nail is more complete, as it measures both platelet function and fibrin stabilization, whereas the template buccal mucosal
bleeding time only assesses the contribution of platelets to the hemostatic plug.] For therapy, the recommended approach is
to transfuse beforehand and complete the surgery within the next 4 hr, the period which confers the maximal platelet adhesive
properties of the transfused vWF. Cryoprecipitate is usually reserved for the severe homozygous affected (zero vWF:Ag) animal
due to cost and availability constraints.
For severe bleeding from quantitative and/or qualitative platelet disorders, freshly prepared platelet-rich plasma
or other platelet enriched concentrate can be given, although these products are not matched for leukocyte and platelet surface
antigens, and could alloimmunize the patient to future transfusions. The prudent approach is to treat the underlying cause,
unless the patient has a heritable platelet defect, and restrict or minimize the use of blood products. Alternative practical
approaches are to give freshly prepared (< 2-3 days old) packed red blood cells which still contain viable platelets (and
leukocytes), or fresh-frozen plasma that contains adhesively active platelet membranes.
[Contributed by W. Jean Dodds, DVM]
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