THROMBOSIS
RESEARCH
Printed in the United States
vol. 7, pp. 825-826, 1975 Pergamon Press, Ino.
LETTER TO THE EDITORS-IN-CHIEF PROTHROMBIN COMPLEX CONCENTRATES AND CHRONIC LIVER DISEASE Rodger L. Bick Department of Medicine, Division of Hematology UCLA Center for the Health Sciences and Bay Area Hematology Oncology Medical Group 1260 Fifteenth Street Santa Monica, California 90404
(Received 21.8.1975. Accepted by Editor Received by Executive Editorial Office
B. Blomback.
16.9.1975.)
Recent meetings of the International Society on Thrombosis and Haemostasis (Paris) and the World Federation of Hemophilia (Helsinki) provided a forum for several strong statements against the use of prothrombin complex concentrates (PCC) in chronic liver disease. Caution and concern regarding some of these opinions seems warranted. There is little question that these concentrates are potentially associated with serious side effects, primarily hepatitis and thrombosis. However, as in all clinical medicine, judgement, rather than isolated side effects, must dictate therapy: one must always weigh prognosis of the disorder being treated and potential benefits of the therapeutic modality against potential hazards of the treatment. It is obvious that PCC should not be used to control minor hypoprothrombinemic bleeds; however, when managing a patient with life-threatening hypoprothrombinemic bleeding of chronic liver disease, which has failed to respond to conventional modalities of therapy, these concentrates may be life-saving. In regards to thrombogenicity of these concentrates, it is remarkable that such wide variability in experience exists;one cannot help but wonder if some of this variability rests with technique of handling the concentrate rather than in the concentrate itself or the patient. We (1) as well as others (2,3,4) have used both native and activated PCC in many patients with chronic liver disease associated with severe hypoprothrombinemic bleeding and no thrombotic complications have been noted. It is significant that in several cases of thrombosis reported following the use of these concentrates, no stability check was performed prior to infusion. It must be appreciated that these concentrates must be handled with caution. 825
826
F'ROTHROMBIN CONCENTMTES
Vo1.7,No.5
In our experience, if stability checks are done on each bottle just prior to. infusion (= 0.1 ml of concentrate added to 1.0 ml of titrated patient plasma and the mixture observed for 5 minutes for evidence of fibrin formation), if the material is used when freshly reconstituted and not allowed to stand at room temperature for long periods, and if the concentrate is administered with caution by an experienced physician, not a nurse, these materials are a reasonably safe and efficacious therapeutic modality for controlling hypoprothrombinemic hemorrhage of chronic liver disease. We have adapted the following general guidelines for the use of PCC in hemorrhage associated with chronic liver disease! There must be fulminant, life-threatening hypoprothrombinemic hemorrhage associated with a diagnosis of chronic liver disease. 2. The hemorrhage must have failed to respond to conventional therapy of gastric lavage, Stengstaken-Blakemore tamponade, infusions of fresh frozen plasma, and use of vasopressin. 3* There must be no laboratory evidence of disseminated intravascular coagulation. There usually must be demonstrable a surgically correctable 4. bleeding point (ruptured varix, hemorrhagic gastritis, or peptic ulcer) so that permanent arrest of bleeding can be surgically attempted after achieving temporary hemostasis with prothrombin complex concentrate. If the above guidelines are followed, these concentrates may be a safe and efficacious therapeutic modality for the control of life-threatening hypoprothrombinemic hemorrhage of chronic liver disease. Until more clinical information is available, these concentrates should not be withheld when their use is indicated: the risk of hepatitis or thrombosis is preferable to that of exsanguination. 1.
REFERENCES 1.
BICK, R.L., SCHMALHORST, W.R., and SHANBROM, E. Prothrombin Complex Concentrates: Use in Controlling the Hemorrhagic Diathesis of Chronic Liver Disease. Am. J. Digestive Dis. 201 741-750, 1975.
2.
GREEN, G., POLLER, L., DYMOCK, I.W., and THOMSON, J.M. Use of Factor VII-Rich Prothrombin Complex Concentrate in Liver Disease. Lancet I: 1311, 1975.
39
DIOGUARDI, N., and MANNUCCI, P.M. Prothrombin Complex Concentrates in Liver Disease. Lancet 28 188, 1975. Experience with a Factor II-IX-X Concentrate (Bebulin): Biochemical Data, in-vivo Recovery, and Clinical Results. Trans X World Federation for Hemophilia, Helsinki, 1975.
4. VINAZZER, H., and BERGMANN, H.
RESEARCH
Printed in the United States
vol. 7, pp. 825-826, 1975 Pergamon Press, Ino.
LETTER TO THE EDITORS-IN-CHIEF PROTHROMBIN COMPLEX CONCENTRATES AND CHRONIC LIVER DISEASE Rodger L. Bick Department of Medicine, Division of Hematology UCLA Center for the Health Sciences and Bay Area Hematology Oncology Medical Group 1260 Fifteenth Street Santa Monica, California 90404
(Received 21.8.1975. Accepted by Editor Received by Executive Editorial Office
B. Blomback.
16.9.1975.)
Recent meetings of the International Society on Thrombosis and Haemostasis (Paris) and the World Federation of Hemophilia (Helsinki) provided a forum for several strong statements against the use of prothrombin complex concentrates (PCC) in chronic liver disease. Caution and concern regarding some of these opinions seems warranted. There is little question that these concentrates are potentially associated with serious side effects, primarily hepatitis and thrombosis. However, as in all clinical medicine, judgement, rather than isolated side effects, must dictate therapy: one must always weigh prognosis of the disorder being treated and potential benefits of the therapeutic modality against potential hazards of the treatment. It is obvious that PCC should not be used to control minor hypoprothrombinemic bleeds; however, when managing a patient with life-threatening hypoprothrombinemic bleeding of chronic liver disease, which has failed to respond to conventional modalities of therapy, these concentrates may be life-saving. In regards to thrombogenicity of these concentrates, it is remarkable that such wide variability in experience exists;one cannot help but wonder if some of this variability rests with technique of handling the concentrate rather than in the concentrate itself or the patient. We (1) as well as others (2,3,4) have used both native and activated PCC in many patients with chronic liver disease associated with severe hypoprothrombinemic bleeding and no thrombotic complications have been noted. It is significant that in several cases of thrombosis reported following the use of these concentrates, no stability check was performed prior to infusion. It must be appreciated that these concentrates must be handled with caution. 825
826
F'ROTHROMBIN CONCENTMTES
Vo1.7,No.5
In our experience, if stability checks are done on each bottle just prior to. infusion (= 0.1 ml of concentrate added to 1.0 ml of titrated patient plasma and the mixture observed for 5 minutes for evidence of fibrin formation), if the material is used when freshly reconstituted and not allowed to stand at room temperature for long periods, and if the concentrate is administered with caution by an experienced physician, not a nurse, these materials are a reasonably safe and efficacious therapeutic modality for controlling hypoprothrombinemic hemorrhage of chronic liver disease. We have adapted the following general guidelines for the use of PCC in hemorrhage associated with chronic liver disease! There must be fulminant, life-threatening hypoprothrombinemic hemorrhage associated with a diagnosis of chronic liver disease. 2. The hemorrhage must have failed to respond to conventional therapy of gastric lavage, Stengstaken-Blakemore tamponade, infusions of fresh frozen plasma, and use of vasopressin. 3* There must be no laboratory evidence of disseminated intravascular coagulation. There usually must be demonstrable a surgically correctable 4. bleeding point (ruptured varix, hemorrhagic gastritis, or peptic ulcer) so that permanent arrest of bleeding can be surgically attempted after achieving temporary hemostasis with prothrombin complex concentrate. If the above guidelines are followed, these concentrates may be a safe and efficacious therapeutic modality for the control of life-threatening hypoprothrombinemic hemorrhage of chronic liver disease. Until more clinical information is available, these concentrates should not be withheld when their use is indicated: the risk of hepatitis or thrombosis is preferable to that of exsanguination. 1.
REFERENCES 1.
BICK, R.L., SCHMALHORST, W.R., and SHANBROM, E. Prothrombin Complex Concentrates: Use in Controlling the Hemorrhagic Diathesis of Chronic Liver Disease. Am. J. Digestive Dis. 201 741-750, 1975.
2.
GREEN, G., POLLER, L., DYMOCK, I.W., and THOMSON, J.M. Use of Factor VII-Rich Prothrombin Complex Concentrate in Liver Disease. Lancet I: 1311, 1975.
39
DIOGUARDI, N., and MANNUCCI, P.M. Prothrombin Complex Concentrates in Liver Disease. Lancet 28 188, 1975. Experience with a Factor II-IX-X Concentrate (Bebulin): Biochemical Data, in-vivo Recovery, and Clinical Results. Trans X World Federation for Hemophilia, Helsinki, 1975.
4. VINAZZER, H., and BERGMANN, H.
