Coagulation

Anticoagulants

Other anticoagulants & thrombolytic therapy



Topic Completed: 1 June 2012

Minor changes: 29 April 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Danaparoid (Orgaran), Hirudin [title], Thrombolytic therapy [title], Warfarin [title] AND Coumadin [title]

Jeremy C. Parsons, M.D.
Page views in 2021 to date: 48
Cite this page: Parsons JC. Other anticoagulants & thrombolytic therapy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationotheranticoagulants.html. Accessed October 18th, 2021.
Danaparoid (Orgaran)

Definition / general
  • Approved to prevent deep venous thromboses
  • Also an alternative to heparin for patients with heparin induced thrombocytopenia (Crit Care 2007;11:R102)
  • Use is decreasing due to newer anticoagulants
  • Composed of low molecular weight glycosaminoglycans (mixture of heparan sulfate, dermatan sulfate and chondroitin sulfate) that primarily inhibit factor Xa, factor IIa to a much lesser extent

Clinical features
  • Similar to low molecular weight heparin in having a more predictable anticoagulant effect, with less need for laboratory monitoring
  • Monitor, if desired, by measuring inhibitor of factor Xa using standard curve; draw 6 hours after subcutaneous injection; PT and PTT are unaffected
  • Therapeutic levels to treat DVT are 0.5 - 0.8 anti-factor Xa units/ml, lower for DVT prophylaxis
  • Long half-life, is prolonged with renal failure
  • No reversal agent is known but incomplete reversal is shown with protamine sulfate
  • Not marketed in the US since 2004, still available in some countries.
Hirudin

Definition / general
  • Anticoagulant approved by FDA to treat thrombosis in patients with heparin induced thrombocytopenia (does not itself cause this type of syndrome)
  • Derivatives include lepirudin, refludan
  • Recombinant protein, cloned from a leech, which directly inhibits factor IIa (thrombin) (Wikipedia: Hirudin [Accessed 19 April 2021])
  • Also has fibrinolytic properties
  • More predictable anticoagulant effect than standard heparin, less need for laboratory monitoring, although close monitoring is still advised with PTT, though this assay has limitations (ecarin clotting time is preferable)
  • Prolongs PT, PTT, thrombin time, ACT and interferes with most clotting based assays
  • Therapeutic range to treat DVT is PTT that is 1.5 - 2.5 x normal but more specific assays are also used to monitor, such as ecarin clotting time
  • Half-life ~1 hour, may be prolonged if antibodies develop, dramatically prolonged in renal failure
  • No reversal agent
  • Reference: Thromb Haemost 2008;99:819
Thrombolytic therapy

Definition / general
  • Used to treat myocardial infarction, pulmonary embolism, arterial or venous thrombosis, thrombotic stroke
  • Thrombolytic agents include recombinant t-PA, urokinase, streptokinase (only tPA is widely available in the USA)
  • Presence of fibrin degradation products and D-dimers, decreased fibrinogen and plasminogen, prolonged thrombin time, PT and PTT
  • References: Clin Lab Med 2009;29:159

Diagrams / tables

Images hosted on other servers:

t-PA action

Warfarin (Coumadin)

Definition / general
  • Therapeutic anticoagulant to prevent thromboembolism by impairing regeneration of active vitamin K (warfarin is a synthetic derivation based on coumarin)
  • Name incorporates the acronym for the organization which funded the key research (WARF) and the ending -arin, indicating its link with coumarin (Wikipedia: Wisconsin Alumni Research Foundation [Accessed 19 April 2021])

Clinical features
  • Takes 4 - 5 days for complete therapeutic effect due to long half-life of factors II and X
  • Must be supplemented with another anticoagulant such as heparin (bridged) until INR is in therapeutic range for 2 consecutive days to prevent Warfarin Skin Necrosis in those with low Protein C
  • Therapeutic effect is measured by INR; goal is often INR between 2 and 3
  • INR may be elevated by lupus anticoagulants or use of hirudin with warfarin
  • Warfarin should not be used alone for acute heparin induced thrombocytopenia because it causes paradoxical thrombosis; must add a rapid acting anticoagulant (hirudin, danaparoid, argatroban) until INR is therapeutic
  • PTT may be normal even if low warfarin levels

Treatment of bleeding / overdose

Diagrams / tables

Images hosted on other servers:

Biochemistry of coumarins

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