Consumption Coagulopathy
and Microangiopathic Hemolytic Anemia
with an Axillo-Femoral Graft
THOMAS J. MYERS, M.D.,
AND
DAVID H. HILD, M.D.
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
SUMMARY Consumption coagulopathy and microangiopathic
hemolytic anemia occurred as a complication of insertion of an axillofemoral, preclotted dacron graft. Treatment with heparin followed
by dipyridamole and aspirin normalized the hematologic and
coagulation abnormalities over a two month period. The mechanism
of consumption coagulopathy associated with prosthetic grafts is discussed and a possible role for treatment with antiplatelet agents is
suggested.
CONSUMPTION COAGULOPATHY is a recognized
complication of a wide variety of diseases." 2 Microangiopathic hemolytic anemia (MAHA) has been frequently
associated with consumption coagulopathy3` as well as
other entities.7 The following case records the occurrence of
consumption coagulopathy and MAHA in a patient with an
axillofemoral dacron graft prosthesis.
erythroid hyperplasia and adequate megakaryocytes and
iron.
The diagnosis of chronic consumption coagulopathy and
MAHA was made and the patient was treated with heparin
4000 units intravenously every four hours for 12 days. The
petechea on his shins promptly cleared and the laboratory
studies improved (table 1). Upon discharge on July 15 treatment with dipyridamole 25 mg three times a day and aspirin
0.6 gm a day was begun. As shown in table 1 his laboratory
studies slowly returned to normal over the next two months.
The dipyridamole was discontinued after one month and the
aspirin after two months. Subsequently the patient's
hematologic and coagulation studies have remained normal
and the graft has maintained good function.
Case Report
On June 13, 1975, a 73-year-old male received an axillofemoral and crossed-femoral bypass with a preclotted,
microknit dacron graft for peripheral vascular disease. Preoperative laboratory studies included a hematocrit of 46%,
white cell count 6500/mm3, platelet count 248,000/mm3,
prothrombin time 11 sec and partial thromboplastin time 29
sec. Intraoperatively two units of packed red cells were given
and a postoperative hematocrit was 38%. The postoperative
course was uncomplicated. During the hospitalization he
received cefazolin, cephalothin, hydroxyzine, diphenhydramine, meperidine and diazepam. On the third postoperative
day his hematocrit was 34% and a platelet estimate was normal. No further laboratory studies were obtained. He was
discharged on the ninth day- without medication.
Eleven days later, 20 days postop, he was readmitted for
left groin suture breakdown. Physical examination revealed
petechea on the soft and hard palate, palpable petechial
lesions over both shins and ankles and bilateral ankle
edema. Laboratory findings included a hematocrit of 26%,
platelet count 23,000/mm3 and corrected reticulocyte count
3%. Coagulation studies revealed a prothrombin time of 14
sec, partial thromboplastin time 36 sec, thrombin time 34
sec (normal 14-23), fibrinogen level 80 mg% (normal
200-500), fibrin split products 1/32 (normal less than l/8),
factor V 100% and factor VIII 75%. Trace amounts of
hemoglobin were found in the urine. A direct and indirect
Coombs test was negative. Stool hematests were negative.
The bilirubin, lactic dehydrogenase, iron, B12 and folic acid
studies were normal. A peripheral smear showed microspherocytes, fragmented erythrocytes and helmet cells (fig.
1). A bone marrow aspirate revealed normal cellularity with
Comments
This patient developed chronic, low-grade consumption
coagulopathy with microangiopathic hemolytic anemia
(MAHA) following the insertion of a preclotted, dacron axillofemoral graft. Three mechanisms have been shown to
trigger consumption coagulopathy:1 1) release of tissue
thromboplastin activating the extrinsic coagulation system,
2) contact of blood with a nonendothelialized surface, activating the intrinsic system and 3) red cell or platelet injury,
releasing procoagulant phospholipids.
Preclotted prosthetic grafts are allowed to have blood clot
on their loose dacron mesh during insertion at surgery.8 9
Contact of blood with this foreign surface produces clotting
through three sequential stages:'0 11 1) adsorption of a protein film layer including fibrinogen and factor XII, 2)
platelet adhesion and aggregation to the adsorbed layer, and
3) fibrin-thrombus-red cell complex formation. The flow surface of a prosthetic graft becomes highly thrombogenic
because of this fibrin-thrombus complex.9 Thrombus will
continue to form on the graft surface unless the velocity of
blood flow exceeds a critical level (thrombotic threshold
velocity),'2 which can dislodge activated clotting factors,
platelets and fibrin
monomers
from the graft wall.8 . 12, 13
Since the length and surface area of most prosthetic grafts
are small, coagulation factor production compensates for
mild increases in utilization -on the graft'3 and clinical consumption coagulopathy is not apparent. However, if the surface area is sufficiently large, consumption will surpass
replacement'3 and clinical consumption coagulopathy may
result, as in the present case.
Other clinical states with vascular endothelial disruptioh4
or foreign surfaces have been associated with consumption
From the Departments of Medicine, The University of Connecticut Health
Center, Farmington, Connecticut, and Hartford Hospital, Hartford, Connec-
ticut.
Address for reprints: David H. Hild, M.D., 100 Retreat Avenue, Hartford,
Connecticut 06106.
Received May 2, 1977; revision accepted June 3, 1977.
891
VOL 56, No 5, NOVEMBER 1977
ClIRCULATION
892
TABLE 1. Laboratory Studies and Treatment
Platelet
PTT
Fibrinogen
(%)
(/mm')
PT
Date
46
Surgery
38
34
248000
(see)
29
(mm%o)
6/12
6/13
6/14
6/16
(see)
11
7/3
26
Ni Est
Ni Est
2300
7/15
31
7/23
8/13
9/14
10/15
Hot
FSP
Ni
80
1/32
40000
135
1/32
32
94000
170
36
36
36
127000
160000
Ni Est
175
200
14
36
1/8
NI
Ni
Frag
RBC
Frag
RBC
Frag
RBC
Ni
Ni
Ni
Abbreviations: NI = normal; Est = estimate; Frag -fragmented; RBC = red blood cells; ASA
prothrombin time; PT T - partial thromboplastin time; FSP = fibrin split products.
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
coagulopathy. These include ruptured or dissecting aortic
aneurysm,14 giant hemangioma,'5 malignant hemangioendotheliomall and cardiopulmonary bypass.2
The consumption coagulopathy in the present case persisted for weeks. Theoretically, with the preclotted graft, the
thrombus lining of the flow surface will be readily organized
and covered with endothelium.8 However, studies of arterial
prostheses in man have shown incomplete organization, with
a persistence of fibrin on the flow surface even after several
years.8, 17 Sauvage et al.12 have suggested that persistent
thrombotic deposition is prevented by a conversion of the
fibrin lining to a fibrin of less thrombogenicity when the
thrombotic threshold velocity is established.
Active thrombogenesis on large prosthetic grafts can also
be associated with microembolization.15 In the present case
the palpable petecheal lesions located on the lower extremities were compatible with microembolic lesions.
Microangiopathic hemolytic anemia occurs frequently
with both localized or generalized consumption coagulopathy.2 e The condition develops when fibrin-attached red
cells are fragmented by the sheering force of the blood
00
F ,
jj_-
N*
0
.
0k
~
.#
,/'
FIGURE 1. Peripheral blood smear showing fragmented
erythrocytes, helmet cells, and microspherocytes.
Treatment
Smear
=
Heparin until
7/15
ASA +
Dipyridamole
ASA +
Dipyridamole
ASA
acetylsalicylic acid; PT =
stream.3' I Crenated and echinocytic red cells enmeshed in
fibrin strands have been found in prosthetic grafts.9 Microangiopathic hemolytic anemia may perpetuate consumption
coagulopathy through release of red cell procoagulant
phospholipids.3
Effective treatment with heparin of both consumption
coagulopathy"' 2 and MAHA1' is recognized. Reduced
platelet survival in patients with aortofemoral grafts has
been demonstrated.20 21 Dipyridamole alone or dipyridamole with aspirin have normalized the platelet survival
time with these grafts.20' 21 The present case suggests
that antiplatelet agents may prevent perpetuation of thrombus formation and consumption coagulopathy in a graft by
blocking continued platelet deposition and procoagulant
phospholipid release.
References
1. Coleman RW, Robboy SJ, Minna JD: Disseminated intravascular
coagulation (DIC): An Approach. Am J Med 52: 679, 1972
2. Bachmann F: Disseminated intravascular coagulation. DM, Dec 1969
3. Rudenberg ML, Regoeczi E, Bull BS, Bacie JU, Brain MC: Microangiopathic haemolytic anaemia: The experimental production of
haemolysis and red cell fragmentation by defibrination in vivo. Br J
Haematol 14: 643, 1968
4. Bull BS, Rudenberg ML, Bacie JV, Brain MC: Microangiopathic
haemolytic anaemia: Mechanisms of red cell fragmentation: in vitro
studies. Br J Haematol 14: 643, 1968
5. Rosner F, Rubenberd ML: Erythrocyte fragmentation in consumption
coagulopathy. N Engl J Med 280: 219, 1969
6. Jacobson RJ, Jackson DP: Erythrocyte fragmentation in defibrination
syndrome. Ann Intern Med 81: 207, 1974
7. Brain MC: Microangiopathic hemolytic anemia. Ann Rev Med 21: 133,
1970
8. Sauvage LR, Berger K, Wood SJ: A very thin, porous, knitted arterial
prosthesis: Experimental data and early clinical assessment. Surgery 65:
78, 1969
9. Gurdoin RG, Gosselin C, Rouleau C: Preclotting of knitted dacron
prosthesis. J Thorac Cardiovasc Surg 70: 152, 1975
10. Dutton RC, Baier RE, Dedrick RL, Bowman RL: Initial thrombus formation on foreign surfaces. Trans Am Soc Artif Intern Organs 14: 57,
1968
11. Dutton RC, Webber AJ, Johnson SA, Baier RE: Microstructure of
initial thrombus formation on foreign materials. J Biomed Mater Res 3:
13, 1969
12. Sauvage LR, Berger KE, Mansfield PB, Wood SJ, Smith IC, Overton
JB: Future directions in the development of arterial prostheses for small
and medium caliber arteries. Surg Clin North Am 54: 213, 1974
13. Salzman EW: Nonthrombogenic surfaces: Critical Review. Blood 38:
509, 1971
14. Cate DW, Timmers H, Becker A: Coagulopathy in ruptured or dissecting aortic aneurysms. Am J Med 59: 171, 1975
GRAFT CONSUMPTION COAGULOPATHY/Myers, Hild
15. Inceman S, Yucel T: Chronic defibrination syndrome due to a giant
hemangioma associated with microangiopathic hemolytic anemia. Am J
Med 46: 987, 1969
16. Benisch BM, Alpert LI: Malignant hemangioendothelioma and consumption coagulopathy. N Engi J Med 285: 804, 1971
17. Berger K, Sauvage LR, Rao AM, Wood SJ: Healing of arterial
prostheses in man: Its incompleteness. Ann Surg 175: 118, 1972
18. Mason RG: The interaction of blood hemostatic elements with artificial
893
surfaces. Prog Hemostasis Thromb 1: 141, 1972
19. Brain MC, Baker LR, McBride JA, Rubenberg ML, Bacie JV: Treatment of patients with microangiopathic haemolytic anaemia with
heparin. Brit J Haematol 15: 603, 1968
20. Slichter SJ, Harker LA, Sauvage LR: Platelet consumption as a measure
of endothelialization of aortofemoral grafts. Blood 40: 938, 1972
21. Harker LA, Slichter SJ: Platelet and fibrinogen consumption in man. N
Engl J Med 297: 999, 1972
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Consumption coagulopathy and microangiopathic hemolytic anemia with an
axillo-femoral graft.
T J Myers and D H Hild
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Circulation. 1977;56:891-893
doi: 10.1161/01.CIR.56.5.891
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1977 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://circ.ahajournals.org/content/56/5/891
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally
published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further
information about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation is online at:
http://circ.ahajournals.org//subscriptions/