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Uri Martinowitz

Publications and source records attributed to Uri Martinowitz.

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Updates in the management of severe coagulopathy in trauma patients.

Coagulopathy is the major cause of bleeding-related mortality in patients who survive the operating room. Its association with hypothermia and metabolic acidosis is common and constitutes a vicious cycle. Usually, post-traumatic coagulopathy is an early event and may be present during surgery. The pathogenesis of severe post-traumatic coagulopathy is complex and multifactorial. Virtually every aspect of the normal coagulation cascade is affected in the cold, acidotic, exsanguinating trauma patient. In the last decade many surgeons have emphasized the role of prevention or early treatment of this vicious cycle. Damage control surgery with planned re-operations has demonstrated superiority over the traditional approach in cases where the patients' condition is deteriorating. Early control of surgical bleeding and significant contamination, together with vigorous correction of hypothermia and continuous resuscitation, has improved the survival of these patients. Recently, a new adjunct to the treatment of coagulopathy in trauma patients has been reported and is undergoing controlled animal trials. Recombinant activated factor VII (rFVIIa) was originally developed as a pro-hemostatic agent for the treatment of bleeding episodes in hemophilia patients. rFVIIa has been successfully used in moribund trauma patients in whom standard procedures had failed to correct bleeding. Preliminary preclinical and clinical studies are under way.

Blood Loss, Surgical↗

Early use of recombinant factor VIIa improves mean arterial pressure and may potentially decrease mortality in experimental hemorrhagic shock: a pilot study.

BACKGROUND: Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and improve survival after experimental hepatic trauma. METHODS: Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction of mean arterial pressure, animals were blindly randomized to receive intravenous rFVIIa (180 microg/kg) (n = 6) or placebo (n = 7). RESULTS: Mortality was 43% (three of seven) in controls versus 0% with rFVIIa (p = 0.08, chi2). Significantly shorter prothrombin time and higher mean arterial pressures were observed in the rFVIIa group. CONCLUSION: Intravenous administration of rFVIIa early after induction of hemorrhage shortens prothrombin time and improves mean arterial pressure. A trend toward improved survival was observed.

Animals↗

Possible role of recombinant activated factor VII (rFVIIa) in the control of hemorrhage associated with massive trauma.

PURPOSE: To report our experience with recombinant activated factor VII (rFVIIa) to control hemorrhage in trauma patients with profound multifactorial coagulopathy. rFVIIa forms a complex with tissue factor exposed at sites of tissue damage and induces activation of coagulation limited to the site of injury. It is approved for use in hemophilia patients, however, its use in trauma is still controversial due to the theoretical risk of thromboembolic complications. CLINICAL FEATURES: Nineteen critically ill, multi-transfused patents with trauma (ten blunt and nine penetrating), aged 25 + 17 yr,were treated with rFVIIa after all conventional hemostatic measures had failed. After one to three doses of rFVIIa, hemorrhaging ceased within minutes in 15/19 (78.9%) patients. The total dose of rFVIIa required to control bleeding was 195 +/- 112.7 microg x kg(-1). Shortening of prothrombin time and partial thromboplastin time was observed within 15-30 min from 22.7 +/- 7.9 to 10.4 +/- 2.6 sec and 71 +/- 38.9 to 42.2 +/- 24 sec respectively, (P < 0.05). Transfusion requirements decreased from 30 +/- 18.3 units used within 5.6 +/- 3.4 hr of admission to 2.8 +/- 2.5 within the following 24 hr (P < 0.05). One patient developed clinical deep vein thrombosis. No systemic activation of coagulation was observed clinically. Thirteen patients (68.4%) survived and recovered. Four patents did not respond to rFVIIa treatment and exsanguinated within 24 hr. Two patients died after one week, one from sepsis and one from multi-organ failure. CONCLUSIONS: rFVIIa is a promising adjunctive hemostatic treatment for trauma patients suffering from massive bleeding. Controlled trials are warranted to evaluate the safety and efficacy of this drug.

Adult↗