Activated Partial Thromboplastin Time In Patients Research Articles

Abstract 9574: Distribution of Anti-Factor Xa Activity Value, Prothrombin Time, and Activated Partial Thromboplastin Time in Patients Treated With Factor Xa Inhibitors

Introduction: The distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) has not fully been assessed. Purpose: To clarify the distribution of AXA, PT, and APTT in patients taking FXa inhibitors. Methods: Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage. Results: At trough time of apixaban, the AXA values in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P < 0.001). PT in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P = 0.006). At peak time, the AXA values in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P < 0.001). PT in patients administered 20 mg was significantly higher than those administered 5 mg or 10 mg (P < 0.001). APTT in patients administered 20 mg was significantly higher than those administered 5 mg or 10 mg (P < 0.001). At peak time of edoxaban, the AXA values in patients administered 60 mg were significantly higher than those administered 15 mg or 30 mg (P < 0.001). PT in patients administered 60 mg were significantly higher than those administered 15 mg or 30 mg (P = 0.006). APTT in patients administered 60 mg was significantly higher than those administered 30 mg (P = 0.003). At trough time of rivaroxaban, the AXA values in patients administered 30 mg were significantly higher than those administered 10 mg or 15 mg (P = 0.001). At peak time, AXA values in patients administered 30 mg were significantly higher than those administered 15 mg (P = 0.028). Conclusion: This study determined the distribution of AXA, PT, and APTT in patients administered apixaban, edoxaban, and rivaroxaban.

Anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time in patients treated with factor Xa inhibitors.

The regimens for factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) vary with venous thromboembolism (VTE) or non-valvular atrial fibrillation (NVAF). The dosage and duration of FXa inhibitor therapy also differ. However, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each FXa inhibitor has not fully been assessed. Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage. Each FXa inhibitor showed various ranges of AXA values, and twice-daily use resulted in higher absolute AXA values than once-daily use. AXA values and PT for 20mg apixaban at both trough and peak times were significantly higher than those for 5mg or 10mg. AXA values for 60mg edoxaban at peak time were significantly higher than those for 15mg or 30mg. AXA values for 30mg of rivaroxaban at both trough and peak times were significantly higher than those for 10mg or 15mg. In a nonlinear regression model of the relationship between AXA and PT or APTT, PT was positively correlated with AXA values for each FXa inhibitor. This study obtained trough and peak levels of AXA, PT, and APTT in patients with VTE or NVAF who were administered apixaban, edoxaban, and rivaroxaban.

Incidence and Related Factors for Low-Extremity Deep Vein Thrombosis in Breast Cancer Patients Who Underwent Surgical Resection: What Do We Know and What Should We Care.

Malignancy, surgical resection, and neoadjuvant and/or adjuvant chemotherapy increase the low-extremity deep vein thrombosis (LDVT) risk in patients with breast cancer, bringing in great physical burdens, disabilities, and worse survivals. However, LDVT in surgical breast cancer patients is scarcely reported. Therefore, this study aimed to evaluate the incidence and related factors for LDVT in these patients. Patients with breast cancer who underwent surgical resection were included. LDVT was examined on the day of discharge and 1 month after the discharge. A total of 491 eligible patients were included, among which 11 (2.2%) patients occurred LDVT. Besides, higher age, history of diabetes mellitus, advanced T and tumor node metastasis (TNM) stages, higher platelet count, and shorter activated partial thromboplastin time (APTT) were correlated with increased LDVT incidence (all p < 0.05). Additionally, higher age [p = 0.004, odds ratio (OR) (95% CI): 1.082 (1.023–1.144)], history of diabetes mellitus [p = 0.003, OR (95% CI): 10.426 (2.219–48.986)], and a higher platelet count [p = 0.008, OR (95% CI): 1.017 (1.004–1.029)] were independent factors for increased LDVT incidence, while higher APTT [p = 0.004, OR (95% CI): 0.636 (0.467–0.866)] was an independent factor for decreased LDVT incidence. Lastly, the risk prediction model involving age, history of diabetes mellitus, platelet count, and APTT showed a good ability to predict LDVT occurrence (area under curve: 0.919, 95% CI: 0.869–0.968). In conclusion, the LDVT incidence is 2.2%, and its independent factors consist of age, history of diabetes mellitus, platelet count, and APTT in patients with breast cancer who underwent surgical resection, which provides evidence for the prevention and surveillance of LDVT in surgical breast cancer.

Effects of regional citrate anticoagulation in continuous veno-venous hemofiltration of severe burn patients

Objective: To investigate the effects of regional citrate anticoagulation in continuous veno-venous hemofiltration (CVVH) of severe burn patients. Methods: A retrospective non-randomized controlled study was conducted. From January 2017 to August 2020, sixty-eight severe burn patients who met the inclusion criteria were treated with CVVH in Affiliated Hospital of Nankai University. According to the different methods of blood anticoagulation in CVVH treatment, patients were divided into citrate group (n=40) and heparin group (n=28). In the citrate group, 32 males and 8 females were (40±18) years old with total burn area of (62±14)% total body surface area (TBSA); in the heparin group, 22 males and 6 females were (38±16) years old with total burn area of (57±20)%TBSA. Creatinine level, C-reactive protein (CRP) value, and urea nitrogen level in serum of patients were recorded at 0 (immediately), 48, and 96 h after CVVH treatment in 2 groups, urea clearance index was calculated based on urea nitrogen level at 0, 48, and 96 h after CVVH treatment in 2 groups, platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) in total coagulation of patients were recorded. The frequency of forced hemofiltration termination caused by adverse reactions such as severe hypocalcemia, aggravated wound bleeding, and new bleeding on non-wound surface of patients was recorded within 96 h of CVVH treatment. The duration of daily CVVH use from the beginning to the end was recorded. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent samples t test, and Bonferroni correction. Results: There were no significant differences in urea nitrogen level, creatinine level, and CRP value in serum of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h after treatment, urea nitrogen level, creatinine level, and CRP value in serum of patients in citrate group were significantly lower than those in heparin group (t=3.366, -2.315, 2.942, -2.657, 2.011, -2.441, P<0.05), and urea clearance index of patients in citrate group was significantly higher than that in heparin group (t=1.017, 2.233, P<0.05). There were no statistically significant differences in PLT, PT, and APTT of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h, PLT of patients in citrate group was significantly higher than that in heparin group (t=-3.417, -4.143, P<0.05 or P<0.01), PT of patients in citrate group was significantly shorter than that in heparin group (t=2.760, -3.655, P<0.01), APTT of patients in citrate group was significantly shorter than that in heparin group (t=3.719, 5.146, P<0.05 or P<0.01). Within 96 h of treatment, there was 1 case of hypocalcemia and 1 case of aggravated wound bleeding resulting in forced hemofiltration termination in citrate group, but there was no new bleeding on non-wound surface; in heparin group, there was no hypocalcemia, but 7 cases of aggravated wound bleeding and 2 cases of new bleeding on non-wound surface (both at the tracheotomy site) resulting in forced hemofiltration termination. The use time of blood purification filter of patients in citrate group was (11.7±4.8) h, obviously longer than (6.6±2.5) h in heparin group (t=3.310, P<0.01). Conclusions: The use of regional citrate anticoagulation in CVVH treatment of severe burn patients has the advantages including little effect on coagulation function and high safety, can effectively prolong the use time of filter and improve the therapeutic effect, but this conclusion still needs to be further verified in clinical application.

Bleeding Versus Thrombotic Tendency in Young Children With Beta-Thalassemia Major.

IntroductionBleeding and thrombotic events are known to occur in beta-thalassemia major (BTM) patients and have been attributed to hepatic iron overload associated with multiple blood transfusions. We evaluated hemostatic parameters in children with BTM who had no previous history of bleeding or thrombotic episodes.Materials and MethodsHemostatic parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation, protein C and S, iron profile, and liver function tests were evaluated in 54 children (median age = 12 months, age range = 4-144 months) with BTM and 15 age and sex-matched controls.ResultsThe mean PT and APTT of patients were significantly higher (P=0.016 and P <.001) than that of controls. Mean protein C, protein S activity and platelet aggregability with adenosine 5-diphosphate (ADP) as an agonist in patients were significantly lower (P <.001, P <.001 and P=0.007, respectively) than that in controls. Mean serum ferritin in BTM children was not significantly elevated to be associated with hepatic dysfunction.ConclusionDeranged hemostatic parameters indicative of bleeding and thrombotic tendencies are observed in BTM children from an early age and may not be solely due to hyperferritinemia-associated hepatic dysfunction. Despite the presence of deranged hemostatic parameters, a state of balance exists between bleeding and thrombosis, and an imbalance may lead to bleeding or thrombotic events at a later age.

The correlation between coagulation function and prognosis in patients with acute respiratory distress syndrome caused by extrapulmonary sepsis or pulmonary infection

Objective: To explore the difference of coagulation function and its correlation with prognosis in patients with acute respiratory distress syndrome (ARDS) caused by extrapulmonary sepsis and pulmonary infection. Methods: ARDS patients caused by extrapulmonary sepsis and pulmonary infection admitted to the ICU were retrospectively analyzed at the First Affiliated Hospital of China Medical University from July 2017 to June 2019. The clinical characteristics were collected including sequential organ failure assessment (SOFA), coagulation parameters [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-Dimer (D-D), fibrinogen degradation product (FDP), antithrombin Ⅲ(AT-Ⅲ), platelet (PLT)], duration of mechanical ventilation, length of stay (LOS) in ICU and 28-day mortality. According to the risk factors, the patients were divided into extrapulmonary sepsis group and pulmonary infection group. The correlation analysis between coagulation parameters and the prognosis of ARDS patients were analyzed by multivariate logistic regression analysis. Results: A total of 268 ARDS patients were screened and 28 cases were excluded. Finally, 240 ARDS patients were enrolled, including 145 caused by extrapulmonary sepsis and 95 by pulmonary infection. PT, INR and APTT in the extrapulmonary sepsis group were significantly higher than those in pulmonary infection group (P<0.05). AT-Ⅲ level was lower than that in pulmonary infection group (P<0.05). Ninty-three patients survived at 28 days in the non-pulmonary sepsis group, the mortality rate was 35.9% (52/145). PT, INR, APTT in patients who died at 28 days were significantly higher than those of the patients who survived (P<0.05), while AT-Ⅲ level was lower than those of the patients who survived (P<0.05). 49 patients survived at 28 days in the pulmonary infection group, the mortality rate was 48.4% (46/95). There was no significant difference in the coagulation parameters between two groups. Multivariate logistic regression analysis showed that SOFA score without PLT(OR=1.210,95%CI 1.067-1.372,P=0.003) and INR (OR=2.408,95%CI 1.007-5.760,P=0.048) were independent risk factors for 28-day mortality in extrapulmonary sepsis group. Coagulation parameters are not independent risk factors for 28-day mortality in ARDS patients related to pulmonary infection. Conclusion: There are significant differences in coagulation function between ARDS patients caused by extrapulmonary sepsis or pulmonary infection. INR is an independent risk factor for 28-day mortality in extrapulmonary sepsis group.

The distribution of anti-factor Xa activity value, PT and APTT at peak and trough times in patients with direct anti-factor Xa inhibitors

Abstract Background Although patients taking direct oral anticoagulants (DOACs) do not require routine coagulation monitoring, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), PT-international normalized ratio (INR) and activated partial thromboplastin time (APTT) in patients on apixaban, edoxaban and rivaroxaban therapy is still not clear. Purpose The aim is to set the standard values of AXA values, PT, PT-INR and APTT in patients using DOACs. Methods We measured AXA, using chromogenic assay with the HemosIL Liquid Heparin kit, PT, PT-INR and APTT at trough and peak times in 224 patients with non-valvular atrial fibrillation and venous thromboembolism, of whom 90 received apixaban, 100 received edoxaban and 34 received rivaroxaban. The peak time was defined as 3 hours after the intake of apixaban or rivaroxaban, and 2 hours after the intake of edoxaban. The trough time was defined as that immediately before the intake. The AXA values, PT, PT-INR and APTT were measured at least 72 hours after the start of treatment. The dosage of DOACs is defined according to the prescribing information in Japan. Results (The order of results below is apixaban, edoxaban and rivaroxaban, respectively.) The average AXA values were 2.29, 0.23 and 0.39 (IU/mL) at trough time, and 3.04, 1.01 and 1.70 (IU/mL) at peak time. The average PT values were 17.9, 12.9 and 13.1 (s) at trough time, and 19.7, 15.5 and 17.5 (s) at peak time. The average PT-INR values were 1.49, 1.07 and 1.08 at trough time, and 1.65, 1.29 and 1.45 at peak time. The average APPT values were 34.5, 31.3 and 32.0 (s) at trough time, and 39.5, 35.9 and 39.8 (s) at peak time. Conclusion Our findings reveal the standard values of AXA, PT, PT-INR and APTT in patients using apixaban, edoxaban and rivaroxaban in each dosage. The DOACs should be changed if the measured value is out of those standard values in 90% confidence interval. Funding Acknowledgement Type of funding source: None

Effects of application of citrate anticoagulation in bedside continuous blood purification of severe burn patients with sepsis

Objective: To investigate the effects of application of citrate anticoagulation in bedside continuous blood purification (CBP) of severe burn patients with sepsis, so as to provide reference for choosing anticoagulants in CBP of these patients. Methods: Thirty severe burn patients with sepsis, conforming to the study criteria, were admitted to our burn intensive care unit from January 2014 to July 2017. Patients were divided into heparin group and citrate group according to computer randomization method, with 15 cases in each group. Patients in two groups all received bedside CBP treatment. Patients in heparin group used local heparin anticoagulation, while patients in citrate group used local citrate anticoagulation. Time of predicted single-time CBP treatment, time of single-time CBP treatment, time of accumulative CBP treatment, and rate of reaching the standard of CBP treatment time were counted. Changes of prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, serum procalcitonin, and C-reactive protein (CRP) of patients before and after treatment were monitored. Hemorrhage in wounds, incision on trachea, and arteriovenous intubation point, and other complications during and after CBP treatment were observed. Data were processed with independent sample t test and chi-square test. Results: (1) Time of predicted single-time CBP treatment of patients in the two groups was equal. Time of single-time CBP treatment and time of accumulative CBP treatment of patients in citrate group were longer than those in heparin group. Rate of reaching the standard of CBP treatment time of patients in citrate group was significantly higher than that in heparin group (χ(2)=16.655, P<0.01). (2) There was no statistically significant difference in PT, APTT, INR, fibrinogen, serum procalcitonin, and CRP of patients in the two groups before CBP treatment (t=0.203, -1.006, 0.203, 0.039, -1.591, -0.824, P>0.05). PT and APTT of patients in citrate group after CBP treatment were (14.2±1.6) and (45±7) s, respectively, significantly shorter than (15.5±1.4) and (53±6) s in heparin group (t=2.395, 3.321, P<0.05 or P<0.01). INR of patients in citrate group after CBP treatment was 1.13±0.12, significantly lower than 1.24±0.12 in heparin group (t=2.395, P<0.05). Fibrinogen of patients in citrate group after CBP treatment was (3.5±0.6) g/L, significantly higher than (3.0±0.6) g/L in heparin group (t=-2.427, P<0.05). Serum procalcitonin and CRP of patients in citrate group after CBP treatment were significantly lower than those in heparin group (t=2.520, 2.710, P<0.05). Decreased degree of serum procalcitonin and CRP of patients in citrate group after CBP treatment were (1.8±0.6) ng/mL and (143±69) mg/L, respectively, significantly higher than (0.9±0.6) ng/mL and (95±50) mg/L in heparin group (t=-4.033, -2.170, P<0.05 or P<0.01). (3) During CBP treatment, patients in heparin group experienced 21 times of exacerbation of wound hemorrhage and 10 times of new hemorrhage, including 2 times of hemorrhage at incision on trachea and 8 times of hemorrhage at arteriovenous intubation point. No exacerbation of hemorrhage or new hemorrhage happened in patients of citrate group. After CBP treatment, no electrolyte disturbance happened in patients of heparin group, but 1 patient in citrate group experienced hypocalcemia. Conclusions: Application of citrate anticoagulation in bedside CBP of severe burn patients with sepsis shows light impact on systematic coagulation status, and can effectively decrease inflammation reaction of burn sepsis with low rate of hemorrhage.

The changes of plasma coagulation function in patients with glioma and its correlation with malignant grade of glioma

Objective: To investigate the changes of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time(TT), fibrinogen(FIB) and platelet counts(PLT) in plasma of patients with glioma, and to explore the correlations between PT, APTT, TT, FIB and PLT with malignant grades of glioma. Methods: One hundred and seventy-two patients with glioma and 47 health controls were investigated in a retrospective analysis. All patients were diagnosed and identified the WHO grade by pathologist after operation. Including 40 cases with glioblastoma multiforme, WHO Ⅳ grade, 45 cases with anaplastic astrocytoma, WHO Ⅲ grade, 46 cases with astrocytoma and oligodendroglia astrocytoma, WHO Ⅱ grade, and 41 cases with pilocytic astrocytoma. Results: PT was significantly shorter in patients with WHO Ⅰ-Ⅳ grade glioma than that in normal controls (P<0.05); APTT was significantly shorter in patients with WHO Ⅲ and Ⅳ grade glioma than that in normal controls and WHO Ⅰ grade glioma patients (P<0.05); FIB of WHO Ⅳ grade glioma was higher than that in normal control and WHO Ⅰ to Ⅲ grade glioma (P<0.05). While, there was no significant difference of TT and PLT among patients with WHO Ⅰ to Ⅳ and normal controls (P>0.05). Spearman correlation analysis showed that there was negative correlation between APTT and WHO grade (r=-0.200, P=0.007) as well as positive correlation between FIB and WHO grade (r=0.175, P=0.020); Pearson linear correlation analysis showed that there was negative correlation between APTT and Ki67 in patients with glioma. Conclusions: the levels of FIB and APTT in patients with glioma were correlated with WHO grade of glioma, and higher FIB, shorter APTT and PT in patients with WHO Ⅳ grade glioma indicated that there exist hypercoagulation states.

Plasma Circulating Levels of Soluble P-Selectin and Thrombospondin-1 (TSP1) Are Elevated in Patients with Cancer and a Shortened Activated Partial Thromboplastin Time (APTT) without Clinical Evidence of Thrombosis: An Inexpensive and Simple Test (APTT) To Be Considered for Its Clinical Value.

There is evidence of shortening of the APTT in patients afflicted with and without cancer, and cancer is a well known underlying condition associated with hypercoagulability. Increased levels of coagulation factors such as VIII, IX, XI, II, and fibrinogen have been demonstrated as independent risk factors for venous thromboembolism (VTE). However, there is evidence that high levels of circulating factor VIII levels are not the only determinant for a shortened APTT (Blood 2004; 104:3631) and likely the same case for the other factors including fibrinogen levels. A shortened APTT in a patient with cancer with no evidence of a thrombotic event could be of clinical value in particular when the cost of measuring individual coagulation factors previously identified as risk factors for VTE would be very high. A lack of understanding of the underlying mechanism leading to a shortened APTT in the absence of VTE limit its clinical use, particularly for the clinical management of the patient presenting at admission with this phenomenon in association with cancer. In this case-control prospective study, we have investigated a potential mechanism associated with a shortened APTT in patients with cancer without evidence of thrombosis. The rationale for this study was a previous observation supporting a functional role of TSP1 in the generation of thrombin on a cell surface (Thrombosis Research 2005; 116: 533). The study was comprised of 69 human subjects subdivided in three separate groups, Group I, was constituted by 23 normal human volunteers, Group II included 23 patients without a shortened APTT and cancer, Group III was comprised of 23 patients with cancer with a shortened APTT (see table). Groups I and II were matched with group III by age and gender. In addition patients in Group II were matched with Group III by the type of cancer. Laboratory measurements included APTT, D-Dimer, soluble E, L, and P-Selectins as well as TSP1. Platelet and neutrophil counts were determined by automated methods. Laboratory measurements demonstrating a significant difference in Group III when compared with Group I and II were P-Selectin and TSP1. These results were independent of the platelet count in Group III. However the significant elevated circulating levels in plasma of P-Selectin in Group III are evidence supporting platelet activation. There was a trend for higher levels of D-Dimer in Group III (P < 0.17) when compared with Group II (P< 0.76), in accordance with previous studies reported in the literature. In summary, this prospective study demonstrates a potential association of a shortened APTT in patients with cancer with elevated circulating levels of soluble P-Selectin and TSP1. Our laboratory is currently investigating in more detail this interesting finding as well as the prospective clinical follow up of patients included in Groups II and III.Plasma DeterminationsParameterGroup IGroup IIGroup IIIP ValueaPTT29.3±2.728.2±2.323±1.00.01sP-Selectin23.2±425.4±944.0±110.001TSP1382±39871±4961246±2950.001Normal Range APTT: 24.2–35.3 seconds

Intramural Hematoma of the Cecum as the Lead Point of Intussusception in an Elderly Patient with Hemophilia A: Report of a Case

Hemophilia A is a congenital bleeding disorder characterized by a deficiency of coagulation factor VIII. Intramural hematoma of the colon is a very rare complication of this disease. We report a case of intramural hematoma of the cecum serving as the lead point of intussusception in a 65-year-old man with hemophilia A. The patient presented with right-sided abdominal pain and bloody stool. Palpation of his abdomen revealed a fist-sized mass. Abdominal computed tomography (CT) showed a circular mass with concentric rings, consistent with an intussuscepted intestine. Because his activated partial thromboplastin time (APTT) was prolonged, we gave him a continuous infusion of factor VIII during and after surgery. Laparotomy revealed an irreducible colo-colic intussusception and we identified a cecal hematoma as the lead point. After an unsuccessful attempt at Hutchinson's maneuver, we performed right colectomy. We report this case to illustrate the necessity of monitoring APTT in patients with hemophilia A who undergo surgery.

Effect of Heparin on Activated Partial Thromboplastin Time in Patients Undergoing Gynecologic or Obstetric Surgery

The exaggerated prolongation of the activated partial thromboplastin time (APTT) by heparin prophylaxis for postoperative thromboembolism may cause bleeding complications. We examined the effects of various doses of unfractionated heparin on the APTT in patients who underwent a gynecologic or obstetric operation. A total of 68 patients who underwent a gynecologic operation (n = 47) or a cesarean section (n = 21) with risk factors for thromboembolism received a continuous intravenous infusion of unfractionated heparin (110–285 IU/kg/day) after surgery until the patient was mobilized the next day. A group of 61 postoperative patients who did not receive heparin served as controls. The APTT was measured in these 129 patients preoperatively and on postoperative day 1. A clinical deep vein thrombosis occurred in only 1 patient, who was in the control group. No bleeding complications occurred in any patient. The percent change in the APTT was significantly correlated with the dose of heparin administered (p < 0.001). Compared with the control group, the mean APTT was not prolonged in the patients who received heparin at 110–149 IU/kg/day. It was prolonged significantly in the patients who received heparin at greater than 150 IU/kg/day. An exaggerated prolongation of the APTT, defined as an APTT greater than 150% of the preoperative value, was found in 0 of 32 patients in the 110–149 IU/kg/day group, 1 of 28 patients (3.6%) in the 150–199 IU/kg/day group and 2 of 8 patients (25%) in the 200–285 IU/kg/day group. The continuous postoperative administration of intravenous heparin at less than 200 IU/kg/day does not result in an exaggerated prolongation of the APTT.

Effect of warfarin on activated partial thromboplastin time in patients receiving heparin.

The activated partial thromboplastin time (APTT) is used to adjust heparin sodium dosage. However, warfarin sodium is often administered concomitantly with heparin and may also affect the APTT and, therefore, heparin dose. We performed a prospective cohort study to quantify the effect of warfarin on the APTT in patients who are being treated with heparin. Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin. The effects of warfarin, as expressed by international normalized ratio and coagulation factor levels, on APTT were determined. Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive. Consequently, warfarin markedly altered the relationship between APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13 had a therapeutic heparin level and 10 had a subtherapeutic heparin level. In patients receiving concomitant heparin and warfarin therapy, APTT reflects the combined effects of both drugs. Because of the marked effect of warfarin on the APTT, decreasing heparin dose in response to a high APTT frequently results in subtherapeutic heparin levels.

Comparison of Two APTT Methods of Monitoring Heparin Therapy: APTT Ratio and Heparin Response of Pooled Normal Plasma

The sensitivity of the reagents for activated partial thromboplastin time (APTT) test varies greatly. Consequently the physicians who prescribe heparin based on certain APTT ratios may order different doses of heparin and produce different levels of anticoagulation in their patients, depending on the sensitivity of APTT reagent used by the laboratory. The authors have been recommending that physicians in their hospital use a therapeutic range for heparinization based on the sensitivity of the APTT reagent and keep the APTT of patients within the range of APTT of pooled normal plasma containing 0.2-0.4 units of heparin per milliliter. Because the patient's response to heparin in vivo may be different from that of pooled normal plasma, the authors planned to compare the effect of these two methods of heparin monitoring on heparin usage and complications of heparin therapy. In a retrospective study, the authors reviewed the hospital records of patients treated with continuous intravenous heparin for the management of thromboembolic disorders during two periods: one period in which the laboratory used an APTT reagent with low in vitro sensitivity to heparin (LSH) and another period in which the authors used an APTT reagent with high sensitivity to heparin (HSH). The authors found that there were no significant differences between the incidence of bleeding or thrombotic complication in the two periods. Furthermore, they found that in both periods, the patients had received similar total doses of heparin during the first 72 hours of therapy. However, as was expected from in vitro sensitivity, the APTT of patients during the LSH period was significantly lower than those during the HSH period. More heparin would have been used during the LSH period compared to the HSH period of physicians were to use the APTT ratio method for monitoring the therapy. The authors conclude that using the therapeutic range for monitoring heparin therapy based on the heparin response of pooled normal plasma will result in a more comparable level of heparinization from year to year and from center to center than by using the APTT ratio method.