Abstract
Abstract 1296
Poster Board I-318
Patients with inherited bleeding disorders undergoing surgery typically receive therapy to correct the deficient factor to a level of ∼1.0 IU/mL. There is a paucity of well-constructed descriptive data quantifying the changes in coagulation that occur in response to surgical stress in normal individuals, however. Additionally, von Willebrand factor (VWF) and factor VIII (FVIII) are acute phase reactants, and thus, supratherapeutic levels of these proteins that might develop in response to the surgical stress would predispose patients to thrombotic events. Aim: With this in mind, our objective was to quantify the changes in hemostatic variables that occur in response to elective orthopedic surgery in normal individuals.
Eligible subjects > 18 years of age undergoing total knee or total hip replacement were recruited. Exclusion criteria included a known bleeding disorder, hormone replacement therapy, use of oral contraceptives or pregnancy. Following informed consent, blood samples were drawn at five time points: 1) baseline - in clinic 1-2 weeks pre-operatively (pre-op), 2) pre-op the morning of surgery – same day admitting center, 3) intra-operatively (intra-op) – 30 minutes after the start of surgery, 4) 30 minutes post-operatively (post-op) - recovery room, and 5) post-op day one (POD 1) – on the ward. Samples were analyzed for complete blood counts (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), FVIII coagulant activity (FVIII:C) and whole blood thromboelastography (TEG) without tissue factor activation. Repeated measures analysis of variance was used to evaluate trends over time; paired samples t-tests were done to maximize the sample size for pairwise comparisons.
37 subjects were recruited (25 females, 12 males) with a mean age of 64 years (range 33 – 87). Means and ranges for all laboratory parameters are displayed in Table 1 in addition to statistical analysis of the change in all variables over the 5 time points. Statistically significant changes were seen in all variables except PTT and TEG angle. In general, VWF and FVIII indices decreased during surgery (presumably due to consumption) and then increased in the post-operative period (presumably due to a stress response). A great deal of variability was seen in post-operative levels of VWF and FVIII between individuals with some showing borderline low levels and some achieving very high levels.
These data establish a baseline on which to reconsider current strategies for the peri-operative management of patients with inherited bleeding disorders, and provide relevant information when considering the relative risks of bleeding or thrombosis associated with surgery.
| . | Baseline mean (range) . | Pre-op mean (range) . | Intra-op mean (range) . | Post-op mean (range) . | POD 1 mean (range) . | p-value (ANOVA)* . |
|---|---|---|---|---|---|---|
| WBC X109/L (4.0 – 10.5) | 6.71 (4.0-10.1) | 6.84 (4.8-10.3) | 5.88 (3.3-9.5) | 9.31 (5.2-20.3) | 8.56 (5.0-13.8) | <0.0001 n=20 |
| Hemoglobin g/L (120 – 160) | 136 (108-160) | 140 (119-157) | 120 (99-140) | 118 (87-146) | 102 (71-126) | <0.0001 n=20 |
| Platelet X109/L (150 – 400) | 265 (160-479) | 273 (168-499) | 226 (97-477) | 241 (158-399) | 211 (124-327) | <0.0001 n=20 |
| PT seconds (12.5 – 15.7) | 13.1 (12.3-13.8) | 14 (12.9-16.9) | 14.1 (13.2-15.4) | 14.5 (13.1-15.9) | <0.0001 n=17 | |
| PTT seconds (23 – 36) | 29 (25-36) | 29 (25-36) | 30 (20-39) | 30 (26-34) | 30 (26-36) | 0.448 n=12 |
| VWF:Ag IU/mL (0.50 – 2.00) | 1.46 (0.5-2.6) | 1.48 (0.55-2.66) | 1.22 (0.5-2.21) | 1.34 (0.54-2.19) | 1.72 (0.62-4.0) | <0.001 n=15 |
| VWF:RCo IU/mL (0.50 – 2.00) | 1.39 (0.57-2.21) | 1.35 (0.57-2.28) | 1.12 (0.53-1.79) | 1.32 (0.49-3.23) | 1.65 (0.71-3.32) | 0.004 n=15 |
| FVIII:C IU/mL (0.50 – 1.50) | 1.33 (0.56-2.69) | 1.31 (0.62-2.91) | 1.01 (0.43-2.77) | 1.38 (0.45-4.29) | 1.54 (0.51-4.50) | <0.0001 n=15 |
| TEG R minutes (9 – 27) | 8.9 (8 – 10.2) | 6.6 (3.7 – 8.2) | 0.042≠ n=4 | |||
| TEG angle degree (22 – 58) | 56 (48 – 62) | 57 (23 – 76) | 0.743≠ n=4 |
| . | Baseline mean (range) . | Pre-op mean (range) . | Intra-op mean (range) . | Post-op mean (range) . | POD 1 mean (range) . | p-value (ANOVA)* . |
|---|---|---|---|---|---|---|
| WBC X109/L (4.0 – 10.5) | 6.71 (4.0-10.1) | 6.84 (4.8-10.3) | 5.88 (3.3-9.5) | 9.31 (5.2-20.3) | 8.56 (5.0-13.8) | <0.0001 n=20 |
| Hemoglobin g/L (120 – 160) | 136 (108-160) | 140 (119-157) | 120 (99-140) | 118 (87-146) | 102 (71-126) | <0.0001 n=20 |
| Platelet X109/L (150 – 400) | 265 (160-479) | 273 (168-499) | 226 (97-477) | 241 (158-399) | 211 (124-327) | <0.0001 n=20 |
| PT seconds (12.5 – 15.7) | 13.1 (12.3-13.8) | 14 (12.9-16.9) | 14.1 (13.2-15.4) | 14.5 (13.1-15.9) | <0.0001 n=17 | |
| PTT seconds (23 – 36) | 29 (25-36) | 29 (25-36) | 30 (20-39) | 30 (26-34) | 30 (26-36) | 0.448 n=12 |
| VWF:Ag IU/mL (0.50 – 2.00) | 1.46 (0.5-2.6) | 1.48 (0.55-2.66) | 1.22 (0.5-2.21) | 1.34 (0.54-2.19) | 1.72 (0.62-4.0) | <0.001 n=15 |
| VWF:RCo IU/mL (0.50 – 2.00) | 1.39 (0.57-2.21) | 1.35 (0.57-2.28) | 1.12 (0.53-1.79) | 1.32 (0.49-3.23) | 1.65 (0.71-3.32) | 0.004 n=15 |
| FVIII:C IU/mL (0.50 – 1.50) | 1.33 (0.56-2.69) | 1.31 (0.62-2.91) | 1.01 (0.43-2.77) | 1.38 (0.45-4.29) | 1.54 (0.51-4.50) | <0.0001 n=15 |
| TEG R minutes (9 – 27) | 8.9 (8 – 10.2) | 6.6 (3.7 – 8.2) | 0.042≠ n=4 | |||
| TEG angle degree (22 – 58) | 56 (48 – 62) | 57 (23 – 76) | 0.743≠ n=4 |
ANOVAs were performed on subjects with complete data sets with n= shown. Results of paired samples t-tests were generally similar (demonstrating a statistically significant difference between the baseline/intra-op, pre-op/intra-op, and intra-op/POD1 time points).
paired samples t-tests.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal