WARFARIN-INDUCED SKIN NECROSIS
Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.[3]:122 Heparin-induced necrosis can develop both at sites of localinjection and - when infused intravenously - in a widespread pattern.[3]:123
In warfarin’s initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors II, IX and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels, it can lead to massive thrombosis with necrosis and gangrene of limbs.
Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of coumarins is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state.[1]
In one third of cases, warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis (blood stream infection) which also involves skin necrosis. These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency,[6][7] activated protein C resistance (Factor V Leiden)[8] and antithrombin III deficiency.[9]
Although the above theory is the most commonly accepted theory, others believe that it is a hypersensitivity reaction or a direct toxic effect.[1]

WARFARIN-INDUCED SKIN NECROSIS

Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.[3]:122 Heparin-induced necrosis can develop both at sites of localinjection and - when infused intravenously - in a widespread pattern.[3]:123

In warfarin’s initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors IIIX and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels, it can lead to massive thrombosis with necrosis and gangrene of limbs.

Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of coumarins is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state.[1]

In one third of cases, warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis (blood stream infection) which also involves skin necrosis. These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency,[6][7] activated protein C resistance (Factor V Leiden)[8] and antithrombin III deficiency.[9]

Although the above theory is the most commonly accepted theory, others believe that it is a hypersensitivity reaction or a direct toxic effect.[1]

  1. sapphirexknight reblogged this from fyeahmedlab
  2. pugglenurse reblogged this from medicalexamination
  3. clerodendrumsplendens reblogged this from fyeahmedlab
  4. kellythepsycho reblogged this from fyeahmedlab
  5. thousandhandbrightskycannon reblogged this from md-admissions
  6. lastnightsmake-up reblogged this from ouremssite
  7. xia-yu-tian reblogged this from fyeahmedlab
  8. biognosis reblogged this from medicalexamination
  9. wmeacham48 reblogged this from ouremssite
  10. katattack21 reblogged this from md-admissions
  11. allesklarornahh reblogged this from ouremssite
  12. ouremssite reblogged this from your-future-nurse
  13. quickmedical reblogged this from md-admissions and added:
    Another reason why Coag-Sense PT/INR tests are important!
  14. shirohayabusa reblogged this from medicalexamination
  15. imperceptibletruth reblogged this from fyeahmedlab and added:
    omgg the infamous warfarin from tox! D:
  16. squaredonut reblogged this from onekookykookie
  17. bi0med reblogged this from medicalexamination
  18. onekookykookie reblogged this from md-admissions
  19. ricksterthinks reblogged this from md-admissions
  20. qvytnguyen reblogged this from your-future-nurse
  21. rural-medic reblogged this from schizoidtemperament
  22. actualjo reblogged this from your-future-nurse
  23. uaortho reblogged this from your-future-nurse
  24. your-future-nurse reblogged this from drpremed
  25. ndnuamsa reblogged this from md-admissions
  26. mylifeaspremed reblogged this from md-admissions
  27. flourandyarn reblogged this from md-admissions
  28. jengoldeneye reblogged this from nursingisinmyblood