Tm, JouRNAL OF UROLOGY Copyright © 1975 by The Williams & Wilkins Co.
Vol. 113, June Printed in U.S.A.
Single Case Reports FACTOR IX DEFICIENCY IN THE NEPHROTIC SYNDROME: STUDIES WITH PROTHROMBIN COMPLEX CONCENTRATE FAZLUR RAHMAN, BLOSSOM ZANGER
AND
ETHAN A. NATELSON*
From the Department of Internal Medicine, Baylor College of Medicine, Houston, Texas
ABSTRACT
A patient manifesting acquired factor IX deficiency in association with the syndrome received prothrombin complex concentrate and demonstrated an accelerated plasma disappearance rate of factors II, IX and X. Amelioration of proteinuria and the plasma coagulation defect followed therapy with corticosteroids and azathioprine. An isolated deficiency of plasma factor IX activity occasionally arises in certain patients with the nephrotic syndrome and may be consequent to urinary loss of the procoagulant. 1. 2 Management of such patients heretofore has not included specific replacement therapy for the coagulation defect, which typically does not result in a clinical bleeding diathesis. Our report concerns a patient with the nephrotic syndrome in whom an unusually severe deficit in factor IX activity prompted infusion of clotting factor concentrate (konyne) prior to a contemplated renal biopsy and afforded a unique opportunity to the plasma half-life of each of the prothrombin complex factors in this disorder, CASE REPORT
A 48-year-old white woman was hospitalized for evaluation of hypertension and proteinuria in the absence of peripheral edema. Laboratory findings on serum included urea nitrogen 12 mg. per 100 ml., creatinine 0.9 mg. per 100 ml., albumin 2.4 mg. per 100 ml. and cholesterol 260 mg. per 100 mL Standard liver function tests and complete blood counts were normal. Total urinary protein was 5 per 24 hours and microscopic examination of urine sediment revealed numerous oval fat bodies. Routine coagulation studies demonstrated prothrom bin time 11.8 seconds, partial thromboplastin time 82 seconds (control value 32 seconds) and fibrinogen 550 mg. per 100 ml. Specific 1-stage
assays for factors VIII, XI and XII gave normal results but factor IX activity repeatedly measured 5 to 8 per cent. In vitro mixing studies of patient and nornwl plasmas failed to provide evidence for a anticoagulant. The patient received intravenous vitamin K 1 but the striking reduction in factor activity remained constant. Each of several urine specimens contained factor IX activity.2 Medical history disclosed no unusual following surgical procedures including tonsillec., tomy, dental extractions, cholecystectorny and hysterectomy, There was no family suggestive of a blood coagulation defect, The patient received 1,000 units of prothrombin complex (konyne) immediately before a scheduled renal biopsy in order to lessen the potential risk significant hemorrhagic complications. In vivo recovery of factor IX activity was not resulting in cancellation of the procedure without additional prothrombin complex infusion Subse, quently, the patient received 60 mg. per day as treatment for proteinuria and buminemia. Lack of improvement after 3 months resulted in the addition of azathioprine a program of low-dose alternate-day corticosteroids. Six months later a reduction was achieved in total urinary protein to 1.2 gm. per day with an increase in serum albumin to 3.5 gm. per 100 ml. and factor IX activity to 18 per cent, The activated thrombopfastin time now was 45 seconds. function studies remain normal Australia antigen are negative.
Accepted for publication November 8, 1974. Supported in part from Grant HL-16938-01 of the Department of Health, Education and Welfare Division of Blood Diseases and Resources, Bethesda, Maryland and United States Public Health Service Grant RR99134. * Requests for reprints: Medical Hematology, The Methodist Hospital, 6516 Bertner, Houston, Texas 77025. 853
MATERIALS AND METHODS
We performed coagulation testing on venous blood collected in plastic syringes and anticoagulated with a 1:10 volume of 3.2 per cent
~--
854 200
RAHMAN, ZANGER AND NATELSON
--.][JI
•---,,,_____·-----•-----•-----------. •X
A ----'
-
~
u
50
"" "~
10
·~·--.
- - . Il[
Konyne 1000 Units
2
0
3
4
6
7
8
9
10
11
12
13
14
TIME I HOURS )
Plasma activity of factors II, VII, IX and X immediately before and serially following infusion of 1,000 prothrombin complex units (konyne).
Plasma half-disappearance time of prothrombin complex factors following infusion of konyne Clotting Factor
Plasma Half-Disappearance Time (hrs.) Patient
Normal
II VII
8
IX
Vol. 113, June Printed in U.S.A.
Single Case Reports FACTOR IX DEFICIENCY IN THE NEPHROTIC SYNDROME: STUDIES WITH PROTHROMBIN COMPLEX CONCENTRATE FAZLUR RAHMAN, BLOSSOM ZANGER
AND
ETHAN A. NATELSON*
From the Department of Internal Medicine, Baylor College of Medicine, Houston, Texas
ABSTRACT
A patient manifesting acquired factor IX deficiency in association with the syndrome received prothrombin complex concentrate and demonstrated an accelerated plasma disappearance rate of factors II, IX and X. Amelioration of proteinuria and the plasma coagulation defect followed therapy with corticosteroids and azathioprine. An isolated deficiency of plasma factor IX activity occasionally arises in certain patients with the nephrotic syndrome and may be consequent to urinary loss of the procoagulant. 1. 2 Management of such patients heretofore has not included specific replacement therapy for the coagulation defect, which typically does not result in a clinical bleeding diathesis. Our report concerns a patient with the nephrotic syndrome in whom an unusually severe deficit in factor IX activity prompted infusion of clotting factor concentrate (konyne) prior to a contemplated renal biopsy and afforded a unique opportunity to the plasma half-life of each of the prothrombin complex factors in this disorder, CASE REPORT
A 48-year-old white woman was hospitalized for evaluation of hypertension and proteinuria in the absence of peripheral edema. Laboratory findings on serum included urea nitrogen 12 mg. per 100 ml., creatinine 0.9 mg. per 100 ml., albumin 2.4 mg. per 100 ml. and cholesterol 260 mg. per 100 mL Standard liver function tests and complete blood counts were normal. Total urinary protein was 5 per 24 hours and microscopic examination of urine sediment revealed numerous oval fat bodies. Routine coagulation studies demonstrated prothrom bin time 11.8 seconds, partial thromboplastin time 82 seconds (control value 32 seconds) and fibrinogen 550 mg. per 100 ml. Specific 1-stage
assays for factors VIII, XI and XII gave normal results but factor IX activity repeatedly measured 5 to 8 per cent. In vitro mixing studies of patient and nornwl plasmas failed to provide evidence for a anticoagulant. The patient received intravenous vitamin K 1 but the striking reduction in factor activity remained constant. Each of several urine specimens contained factor IX activity.2 Medical history disclosed no unusual following surgical procedures including tonsillec., tomy, dental extractions, cholecystectorny and hysterectomy, There was no family suggestive of a blood coagulation defect, The patient received 1,000 units of prothrombin complex (konyne) immediately before a scheduled renal biopsy in order to lessen the potential risk significant hemorrhagic complications. In vivo recovery of factor IX activity was not resulting in cancellation of the procedure without additional prothrombin complex infusion Subse, quently, the patient received 60 mg. per day as treatment for proteinuria and buminemia. Lack of improvement after 3 months resulted in the addition of azathioprine a program of low-dose alternate-day corticosteroids. Six months later a reduction was achieved in total urinary protein to 1.2 gm. per day with an increase in serum albumin to 3.5 gm. per 100 ml. and factor IX activity to 18 per cent, The activated thrombopfastin time now was 45 seconds. function studies remain normal Australia antigen are negative.
Accepted for publication November 8, 1974. Supported in part from Grant HL-16938-01 of the Department of Health, Education and Welfare Division of Blood Diseases and Resources, Bethesda, Maryland and United States Public Health Service Grant RR99134. * Requests for reprints: Medical Hematology, The Methodist Hospital, 6516 Bertner, Houston, Texas 77025. 853
MATERIALS AND METHODS
We performed coagulation testing on venous blood collected in plastic syringes and anticoagulated with a 1:10 volume of 3.2 per cent
~--
854 200
RAHMAN, ZANGER AND NATELSON
--.][JI
•---,,,_____·-----•-----•-----------. •X
A ----'
-
~
u
50
"" "~
10
·~·--.
- - . Il[
Konyne 1000 Units
2
0
3
4
6
7
8
9
10
11
12
13
14
TIME I HOURS )
Plasma activity of factors II, VII, IX and X immediately before and serially following infusion of 1,000 prothrombin complex units (konyne).
Plasma half-disappearance time of prothrombin complex factors following infusion of konyne Clotting Factor
Plasma Half-Disappearance Time (hrs.) Patient
Normal
II VII
8
IX
