| Comparative Coagulation |
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Testing Services - FAQ's on heparin
therapy
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How does heparin act as an anticoagulant? |
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| Unfractionated (UFH) and low molecular weight (LMW)
heparin act by greatly enhancing the activity of plasma antithrombin,
the major physiologic coagulation inhibitor. Clotting Factor IIa (thrombin)
and Factor Xa are most sensitive to inactivation by heparin-antithrombin
complexes. |
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What are the indications for heparin therapy? |
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In human medicine, heparin therapy is used in the following syndromes: |
Venous thrombosis and pulmonary embolism-
Myocardial infarction, mural thrombosis, unstable angina
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Prevention of thrombosis post-thrombolysis and in extracorporeal
perfusion procedures
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Selected cases of disseminated intravascular coagulation
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Controlled, multi-center, prospective studies of heparin therapy in
animal disease syndromes have not been performed. Clinical uses of
heparin in small animal medicine include the following: |
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Cardiac, aortic, and arterial thrombosis
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Pulmonary thrombosis and thromboembolism
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Disseminated intravascular coagulation
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"Hypercoagulability" associated with IMHA, pancreatitis,
neoplasia, protein losing disorders
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What is an appropriate dosage regimen of heparin? |
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Human dosage guidelines: |
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Unfractionated heparin (UFH): High dose = 400 to 800 U/kg/24 hr;
Low dose = 200 to 300 U/kg/24 hr
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LMW (Dalteparin, Enoxaparin): High dose = 100 U/kg/12h; Low dose
= 2,000 to 5,000 U/adult
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Heparin dosage recommendations vary widely in the veterinary literature.
Adaptation of human dosage guidelines and close monitoring of
each patient seem appropriate pending controlled clinical safety
and efficacy studies in veterinary patients.
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How can I monitor heparin therapy? |
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Three methods of monitoring are available: Clinical status, clotting
time tests, heparin anti-Xa activity |
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All patients should be closely examined to detect disease progression,
or signs of bleeding and bruising, the major complication of heparin
therapy.
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Clotting time tests (ACT and aPTT) assess UFH anticoagulant effect,
and are most often used to detect excess anticoagulation before
clinical signs develop. Target prolongation for high dose UFH
therapy is 1.5X to 2X clotting time of the patient's baseline
or laboratory mean. Clotting time tests are not useful for monitoring
LMW therapy.
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Heparin levels in the therapeutic range (UFH = 0.35 to 0.7 U/ml;
LMW = 0.5 to 1 U/ml) are the best measures of safety and efficacy
in human studies.
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When should samples be drawn for coagulation and heparin assays? |
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| Heparin's peak levels can be detected in samples
drawn 4 hours after injection (IV or SQ intermittent dose). Trough
levels are measured by sampling just before next scheduled dose. |
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What is a heparin sensitivity curve? |
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| A heparin sensitivity curve is established by measuring
the aPTT throughout a range of UFH concentrations. Heparin (UFH) sensitivity
varies for different aPTT assay systems. This example depicts values
for the Comparative Coagulation Laboratory's aPTT assay system. Values
encompassing the therapeutic heparin range of 0.35 to 0.7 U/ml are
shaded. |
| Heparin Activity (U/ml ) |
Canine aPTT (seconds) |
| 0 |
12.6 |
| 0.125 |
14.0 |
| 0.25 |
16.5 |
| 0.50 |
21.0 |
| 0.75 |
36.0 |
| 1.0 |
59.5 |
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What is the difference between UFH and LMW heparin? |
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| Pharmaceutical preparations of unfractionated heparin
(UFH) are derived from porcine or bovine tissues. These preparations
contain high and low molecular weight forms, with variable anticoagulant
activity. Low molecular weight (LMW) heparins are newer drugs, derived
from UFH by means of controlled depolymerization. Both UFH and LMW
heparins act via antithrombin, however one feature of LMW heparin
is a more predictable pharmacologic profile. LMW, in therapeutic dosages,
will not prolong in vitro clotting time tests. Monitoring LMW levels
requires determination of anti-Xa activity. |
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Where can I find more information on heparin therapy? |
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| Please call the Comparative Coagulation Section laboratory
(607-275-0622) for any specific questions on test method or test interpretation. |
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Additional reading: |
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Mischke RH, Schuttert C, Grebe. Anticoagulant effects of repeated
subcutaneous injections of high doses of unfractionated heparin
in healthy dogs. AJVR 2001;62:1887-1891.
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Smith SA, Lewis DC, Kellerman DL. Adjustment of intermittent subcutaneous
heparin therapy based on chromogenic heparin assay in 9 cats with
thromboembolic disease. (abstr) JVIM 1998; 200
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Kellerman DL. Heparin therapy: what we do and don't know. Proceedings
16th ACVIM Forum 1998;438-439.
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Human literature: |
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Diuguid DL. Choosing a parenteral anticoagulant agent. NEJM 2001;345:1340-1341.
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Hirsh J. Heparin. NEJM 1991;324:1565-1574.
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