Platelet Aggregability After Splenectomy in Patients with Normosplenism and Hypersplenism Naofumi Nagasue, MD, Fukuoka, Japan Kiyoshi Inokuchi, MD, PhD, Fukuoka, Japan Michio Kobayashi, MD, Fukuoka, Japan Ryoichi Kanashima, MD, Fukuoka, Japan
It is well known that asymptomatic reactive thrombocytosis after splenectomy occasionally induces thromboembolic complications, such as thrombophlebitis of the extremities or other places, pulmonary infarction, or thrombosis of the mesenteric venous system. The risk of postsplenectomy thrombocytosis usually reaches a peak during the first several weeks after the operation [I], although thrombocytosis may not be the sole factor predisposing to the thromboembolism. However, it has not yet been clarified whether or not postsplenectomy thrombocytosis is really and always associated with an increase in platelet function. On the other hand, it must also be determined whether or not hypercoagulability of the blood takes place after splenectomy in addition to the abnormality of the platelet count. This seems unlikely according to the recent study by Butler et al [2]. In the present study the relationship between platelet count and aggregability after splenectomy in patients with normosplenism and hypersplenism was serially evaluated. The results were compared with those found in patients undergoing upper abdominal surgery.
subdivided into the following three groups: group I, nir e patients with portal hypertension and hypersplenism (Table I); group II, four patients with idiopathic thrombocytopenic purpura (Table II); group III, three patients with normosplenism (Table III). Of the seven control patients (group IV), only six had malignancies, but all underwent radical operations. (Table IV.) Any drug or solution which may have affected platelet function was not administered during the investigation. Blood samples were taken via the veins of the forearm without tourniquet after the patients fasted and rested for at least several hours. Hematocrit, hemoglobin, red blood cell, and white blood cell levels were measured with an automated analyzer. Platelet count was determined with the direct method. The screen filtration pressure method devised by Swank [3] was utilized for the measurement of platelet aggregability. Citrated venous blood was used to determine the screen filtration pressure within 30 minutes after venipuncture. The measurements were performed with and without adenosine diphosphate. The results obtained were corrected according to the hematocrit values, as described by Swank and Davis [4]. All measurements were performed prior to, and one, two, and three weeks after operation. All statistical comparisons for significance were carried out according to Student’s t test, and a p value of less than 0.05 was considered significant.
Material and Methods Results The number and aggregability of platelets were followed in sixteen patients undergoing splenectomy and seven patients undergoing laparotomy. The sixteen patients were
From the Second Department of Surgery, Kyushu University School of Medicine, Fukuoka, Japan. Reprint requests should be addressed to Naofumi Nagasue, MD, Department of Surgery, Kyushu University Hospital, Fukuoka 812, Japan.
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In the patients with portal hypertension and hypersplenism (group I), platelet counts were elevated for all postoperative measurements compared with the preoperative values (p
The American Journal of Surgery
Platelet Aggregability After Splenectomy
TABLE I -.____
Details of Patients with Portal Hypertension and Hypersplenism in Splenectomy Series
Plateletcount - Patient
Sex/Age (yr)
Diagnosis
F/41 M/48 Mf3a Ml41 F/59 F/60 F/35 Ml46 F/59
Cirrhosis of the liver Cirrhosis of the liver Cirrhosis of the liver Cirrhosis of the liver Idiopathic portal hypertension Idiopathic portal hypertension Idiopathic portal hypertension Idiopathic portal hypertension Preheoatic oortal obstruction
--
Operation Splenectomy Splenectomy Splenectomy Splenectomy Splenectomy Splenectomy Splenectomy Splenectomy Solenectomv
+ + + + + + +
SFP with ADP
(X 104) Preop Postop LGCS LGCS LGCS LGCS LGCS LGCS LGCS
+ LGCS
2.4 a.3 6.3 11.7 7.2 11.3 5.2 14.3 5.7
26.4 37.5 47.9 50.0 44.9 48 9 70.0 31.0 410
12 6 30 57 27 31 35 29 55
65 140 >225 200 200 171 >225 200 >225
Note: LGCS = left gastric vena caval shunt; SFP = screen filtration pressure; ADP = adenosine diphosphate
the platelet counts (p <0.05 at 1 week; p X0.001 at 2 and 3 weeks). (Figure 1.) In the four patients with idiopathic thrombocytopenic purpura (group II), only a transient increase in platelet counts was found after splenectomy, with a peak increase on the seventh day. In three of these patients, the screen filtration pressure changed coincidentally with the platelet counts. However, in o.ne patient the aggregability was still markedly elevated two and three weeks after splenectomy, when the platelet counts were already decreasing. (Figure 2.) In the three patients with normosplenism (group II-I), the postoperative changes in both platelet counts and aggregability were principally the same as those seen in group I. (Figure 3.) In the seven patients who had undergone laparotomy (group IV), the platelet counts increased as well, with a peak increase two weeks after operation (p CO.01). However, the screen filtration pressure did not change substantially throughout the period of observation. (Figure 4.) The preoperative mean value of the screen filtration pressure in group I was lower than that in the patients with normal splenic function (group IV) (p CO.01). On the contrary, the former group showed higher values than did the latter group two weeks (p KO.05) and three weeks (p CO.001) after operation. TABLE Ii
Clinical Course. All the patients were carefully checked clinically for postoperation thromboembolic complications. Among the nine patients of group I, thrombophlebitis of the right lower extremity (although a venous graft was taken from the same leg) was encountered in one patient (patient 7) in whom the maximum platelet count was 700,000/mm3 on the fourteenth postoperative day. The screen filtration pressure remained markedly elevated throughout the postoperative weeks, with a peak increase on the fourteenth day. In another instance (patient 5), remittent fever persisted for one month without obvious evidence of infection. Diarrhea with positive occult blood was seen, and venography performed three weeks after operation demonstrated shunt occlusion. In patients of groups II and III, no symptoms and signs of thromboembolism were confirmed postoperatively, although some of them showed a prominent increase in platelet aggregability. Such complications were not seen in the patients without splenectomy (group IV). Comments
In the present study, we investigated the correlation of platelet count to platelet aggregability after splenectomy in patients with the several kinds of diseases for which splenectomy is necessary. The
Details of Patients with idiopathic Thrombocytopenic Purpura in Splenectomy Series TABLE Ill Sex/
Details of Patients with Normosplenism in Splenectomy Series
Age _Patient
(yr)
Diagnosis
Operation
Patient
1
F/21
Splenectomy
1
F/48
Gastric cancer
2
F/40
2
Ml64
Gastric cancer
3
F/43
4
F/20
Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura
3
Ml31
Hereditary spherocytosis
-
Volume 136, August 1978
Sex/Age (yr)
Diagnosis
Splenectomy Splenectomy Splenectomy
Operation Splenectomy + total gastrectomy Splenectomy + total gastrectomy Splenectomy
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Nagasue et al
TABLE IV
Details of Patients with Normosplenism in Laparotomy Series
Patient
Sex/Age (yr)
Diagnosis
1 2 3 4 5 6 7
F/59 F/66 Ml72 Ml63 Ml73 MI41 MI65
Gastric cancer Gastric cancer Gastric cancer Gastric cancer Gastric cancer Duodenal ulcer Esophageal cancer
Platelet count (X 104) Preop Postop
Operation Partial gastrectomy Partial gastrectomy Partial gastrectomy Partial gastrectomy Partial gastrectomy Partial gastrectomy Resection + reconstruction
16.2 19.3 24.8 19.7 13.2 29.1 22.2
31.7 46.0 48.9 20.3 31.1 47.9 39.3
SFP with ADP (mm Hg) Preop Postop 150 69 88 27 66 91 60
66 42 >225 102 121 95 70
Note: SFP = screen filtration pressure; ADP = adenosine diphosphate.
results indicated several important factors. First, the preoperative platelet count and aggregability are significantly suppressed in patients with cirrhosis of the liver, idiopathic portal hypertension (Banti’s syndrome), and prehepatic portal obstruction (group I). This is consistent with the observations made by Thomas, Ream, and Stuart [5] and Ballard and Marcus [6]. However, the platelet aggregability of these patients markedly increased in accordance with the platelet counts after splenectomy. The recognition of this fact may be extremely important when a patient of this group is to be operated on for esophageal varices or hypersplenism. The possibility of shunt occlusion may be higher after proximal splenorenal shunting if no anticoagulants are given when platelet count and aggregability are pathologically elevated. In fact, one of our patients undergoing left gastric vena caval shunting had thrombosis of the shunt. Also, a combination of portal hypertension
250
0.
my Hg
Spletieclomy
I
4 3 x lo/mm
mm Hg
&!
and increased aggregability may enhance the possibility of mesenteric venous thrombosis especially in splenectomized patients [7]. Second, platelet aggregability increased concomitantly with the increase in platelet counts in the patients with normosplenism. This finding disagrees with the observations made by McClure et al [8] and Zucker and Mielke [9]. These authors did not find any increase in platelet function in patients with reactive throm-
50 -o-
SFP. ADPk)
-.-
SFP. ADPt+l
...+..
Platelet(mean)
’ 0
50-
‘3NO.4
$No. 3 No.2
1 I Time
I 2 in Weeks
’ 3
0 Time
Figure 1. Changes (mean f SD) in p/ate/et count and screen flttration pressure (SFP) with and w/ttxnd aden@sfne d@hosphate ( ADP) in nine spknectomy patients with portar hypertension and hyperspienkm.
262
in Weeks
Figure 2. Changes In p/ate/et count and screen filtraflon pressure with adenoshbe d/phosphate In four sp/enectomy patients wffh idlopathk thrombocytopenic purpura.
The American Journal of Surgery
Platelet Aggregability After Splenectomy
bocytosis after splenectomy compared with that in healthy control patients. The cause for this discrepancy is unknown. Third, the platelet function was not always reflected by the platelet count in the patients with idiopathic thrombocytopenic purpura. This result seems to support the well known clinical fact that platelet count often does not correlate with hemorrhagic diathesis in patients with this difficult dosease. Accordingly, serial determination of platelet function might be essentially important to judge whether or not splenectomy has been carried out with real effect in a patient with idiopathic thrombocytopenic purpura. On the other hand, in the control patients undergoing upper abdominal surgery, the platelet count significantly increased two weeks after laparotomy. But the mean value of the screen filtration pressure did not substantially differ from the preoperative value. Thus, the nature of thrombocytosis after splenectomy is different from that after a usual operation. In the former condition, platelet aggregability seems to increase, but not in the latter. Thus, we observed that platelet aggregability increases in accordance with the degree of reactive thrombocytosis after splenectomy under several surgical conditions in patients with or without hypersplenism. However, the present study did not elucidate which of the patients with an increased platelet function may really have a thromboembolic complication. There seems to be no appropriate test for this. Many experimental and clinical observations suggest that additional factors such as hypotension, acidosis, or stagnant blood flow may more easily induce thrombotic complications in the presence of an increased platelet function. Therefore, it may be important to avoid these conditions during the peak period of reactive thrombocytosis. We assume now that during this period the temporary use of proper anticoagulants or inhibitors of platelet aggregation is rational, especially when the patient already has a predisposing condition, such as severe portal hypertension or arteriosclerosis.
a 225 mmHa
Oi x
IO/mm
70r
I
I
O0
I
I
I
1
2
3
Time
in Weeks
Figure 3. Changes in p/ate/et count and screen filtration pressure wffh adenoslne d&hosphate in three splenectomy patients with normosplenlsm.
-o-
SFP. ADPI-I
-*-
SFP. ADPI+\
200
Summary
The relationship between platelet count and aggregability was serially evaluated after splenectomy in patients with normosplenism and hypersplenism, and the results were compared with those found in patients undergoing only upper abdominal surgery. The preoperative count and aggregability of platelets were significantly suppressed in patients with cirrhosis of the liver, idiopathic portal hypertension, and prehepatic portal obstruction. However,
Volume 136, August 1976
I
2
1 Time
3
in Weeks
Figure 4. Changes (mean f SD) in platelet count and screen fillration pressure (SFP) with and wtthout adenoslne dlphosphate (ADP) In seven laparotomy patlents.
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Nagasue et al
the platelet aggregability of these patients markedly increased in accordance with the platelet counts after splenectomy. In the patients with normal splenic function preoperatively, splenectomy caused a simultaneous increase in platelet count and aggregability. The platelet function was not always reflected by the count in the patients with idiopathic thrombocytopenic purpura. On the other hand, in the control patients undergoing only laparotomy the platelet count substantially increased two weeks after operation, but platelet aggregability did not differ from the preoperative value. The present results suggest that additional factors for thromboembolism such as hypotension, acidosis, or stagnant blood flow should be avoided during the peak period of reactive thrombocytosis after splenectomy, and that an appropriate use of anticoagulants or inhibitors of platelet aggregation is recommended if and when necessary.
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References 1. Sedgwick CE, Hume AH: Elective splenectomy: an analysis of 220 operations. Ann Surg 151: 163, 1960. 2. Butler f&J, Britton BJ, Hawkey C, et al: The coagulation and fib$lytt7;esponse to splenectorny. Surg Gyneco/ Obstet142: 3. SwankRL: The screen filtration pressure method in platelet research: significance and interpretation. Serum Hem&o/ 1: 146, 1966. 4. Swank RL, Davis E: Blood cell aggregation and screen filtration pressure. Circ Res 33: 617, 1966. 5. Thomas DP, Ream VJ, Stuart RK: Platelet aggregation in patients with Laennec’s cirrhosis of the liver. N En@ J Mad 276: 1344, 1967. 6. Ballard HS, Marcus AJ: Platelet aggregation in portal cirrhosis. Arch Intern h4ed136: 316, 1976. 7. Case Records of the Massachusetts General Hospital: case 66. N Engl J AMI 267: 719, 1962. 8. McClure PD, Ingram GlC, Stacey RS, et al: Platelet function tests in thrombocythaemia and thrombocytosis. 13rJ Heemetoll2: 478, 1966. 9. Zucker S, Mielke CH: Classification of thrombocytosis based on platelet function tests: correlation with hemorrhagic and thrombotic complications. J Lab C/in Med 80: 385, 1972.
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