Presentation on theme: "Irrational Exuberance: Component Therapy Before Bedside Procedures Jeannie Callum, BA, MD, FRCPC, CTBS Sunnybrook Health Sciences Centre Associate Professor,"— Presentation transcript:
Irrational Exuberance: Component Therapy Before Bedside Procedures Jeannie Callum, BA, MD, FRCPC, CTBS Sunnybrook Health Sciences Centre Associate Professor, University of Toronto
Outline 3 recent papers Bedside procedures and the evidence: Central venous catheters Liver biopsy Thoracentesis & Paracentesis Bronchoscopy &Transbronchial biopsy Renal Biopsy Epidural/Lumbar puncture
Incidence of bleeding after 15,181 percutaneous biopsies and the role of ASA Am J Radiology 2010; 194: 784-789. Mayo Clinic - January 2002 through February 2008 Solid organ percutaneous biopsies 5,832 Kidney biopsies 3,636 Liver biopsies 1,174 Lung biopsies 384 Pancreas biopsies 4,155 Other biospies
Incidence of bleeding after 15,181 percutaneous biopsies and the role of ASA Am J Radiology 2010; 194: 784-789. Local practice at the Mayo clinic: Platelets >50 INR<1.6 Primary endpoint was major bleeding within 3 months of the procedure Major bleeding = RBC transfusion, interventional radiology procedure, operative procedure Follow-up at 3 months was available for 95% of the patients
Incidence of bleeding after 15,181 percutaneous biopsies and the role of ASA Am J Radiology 2010; 194: 784-789. Of 15,181 biopsies, 70 bleeding complications (0.5%) within 3 months, including three deaths (3/15,181, 0.02%) Of the 70 patients with bleeding compared with the remaining patients, the platelet count was lower (194 vs. 257; p <0.001) and the INR was higher (1.2 and 1.0; p < 0.001) No statistically significant difference in the major bleeding complication rates was seen between patients who took aspirin (within 10 days) compared with those who did not (p = 0.34)
Large-bore tunneled central venous catheter insertion in patients with coagulopathy. Haas B, Chittams JL, and Trerotola SO. J Vasc Interv Radiol 2010; 21: 212-217. The Society of Interventional Radiology (SIR), recommend that one needs an INR of 1.5 and a platelet count of 50,000/µL for an ultrasound- guided line placement Single center report from the University of Pennsylvania Medical Center Reviewed the outcomes of 3,170 tunneled central venous catheter placements in 2,514 unique patients
Large-bore tunneled central venous catheter insertion in patients with coagulopathy. Haas B, Chittams JL, and Trerotola SO. J Vasc Interv Radiol 2010; 21: 212-217. Their guidelines: Plt count >25 and INR<2 (although some clinicians tolerated even more abnormal numbers) All performed under ultrasound guidance Patients excluded from the analysis if they had received FFP or platelets between their last set of laboratory values and the procedure Objectives: Primary-incidence of bleeding in first 24 hours Secondary-incidence of infection and catheter failure
Large-bore tunneled central venous catheter insertion in patients with coagulopathy. Haas B, Chittams JL, and Trerotola SO. J Vasc Interv Radiol 2010; 21: 212-217. 567 were placed in patients with platelet counts below 50,000/µL and/or an INR>1.5 They had 27 complications out of 3,170 insertions (1 in 117) 3 of 567 patients with abnormal laboratory numbers developed complications, of which none were hemorrhagic (1 in 189) 3 bleeding complications (1 in 1057), all with platelet counts above 50,000/µL and INR<1.5
Large-bore tunneled central venous catheter insertion in patients with coagulopathy. Haas B, Chittams JL, and Trerotola SO. J Vasc Interv Radiol 2010; 21: 212-217. 99 patients had platelet counts below 30 and 71 had INRs >1.9 at the time of the procedure, suggesting many of their clinicians feel comfortable doing these procedures with more abnormal laboratory values The lowest platelet count was 3 and the highest INR was 3.8 Despite these very abnormal laboratory test results, the complication rate in this group with abnormal laboratory results was identical to that of patients with more normal laboratory numbers
Large-bore tunneled central venous catheter insertion in patients with coagulopathy. Haas B, Chittams JL, and Trerotola SO. J Vasc Interv Radiol 2010; 21: 212-217. If this institution had followed the Society of Interventional Radiology guidelines: They would have needless transfused 300 patients platelets, 282 patients FFP, and 44 both products This translates into approximately 344 adult doses of platelets and 1304 units of FFP administered needlessly
Recombinant factor VIIa for the correction of coagulopathy before emergency craniotomy in blunt trauma patients J Trauma 2010; 68: 348-52. 28 coagulopathic patients in Austin, Texas Aka borderline laboratory abnormalities (defined as an INR>1.3) 75% had subdural hematomas Compared 14 patients that got r7a with the 14 that did not (Not randomized!) – 1.2 mg! rFVIIa group was older (59 vs 41, p 0.04) rFVIIa group was more likely to be on warfarin (57 vs. 14%, p 0.05) no statistical difference in admission INR (rFVIIa 2.6 vs. no- rFVIIa 1.9, p 0.10)
Recombinant factor VIIa for the correction of coagulopathy before emergency craniotomy in blunt trauma patients J Trauma 2010; 68: 348-52. There were no thromboembolic complications in either group There were 7deaths (50%) in the rFVIIa group and 4 deaths (29%) in the no-rFVIIa group (p =0.22)
Recombinant factor VIIa for the correction of coagulopathy before emergency craniotomy in blunt trauma patients J Trauma 2010; 68: 348-52.
Prothrombin complex concentrate vs rVIIa for reversal of coumarin anticoagulation Dickneite G. Thrombosis Res 2006; Jul 12: Epub ahead of print
Prothrombin complex concentrate vs rVIIa for reversal of coumarin anticoagulation
Exploratory study on the reversal of warfarin with rFVIIa in healthy subjects Blood Epub April12, 2010 NBT preBT post warfBT post treatment Placebo2418.729.526.3 40 ug/kg1220.732.328.9 80 ug/kg2418.631.927.7 NPT prePT post warfPT post treatment Placebo2413.027.326.7 40 ug/kg1212.926.814.7 80 ug/kg2413.330.415.0 Bleeding Time (same results for blood loss) PT
INR and aPTT do NOT predict which patient will bleed Segal et al. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion. 2005;45:1413-25
Eckman MH, Erban JK, Singh SK, Kao GS. Screening for the risk for bleeding or thrombosis. Ann Intern Med 2003; 138: W15-W24. 17 studies Role of PT and aPTT in predicting post-operative hemorrhage For nonsurgical and surgical patients without synthetic liver dysfunction or a history of oral anticoagulant use, routine testing has no benefit in assessment of bleeding risk.
BleedNo BleedRate PT elevated22411 in 121 PT not elevated2315611 in 68 All Patients2518021 in 72
FFP given before a procedure will not correct an INR <2
The relationship between the INR and coagulation factors 50 % 30 % 100 % INR11.72.02.23.01.3 zone of normal hemostasis zone of anticoagulation 15 ml/kg FFP 60 ml/kg FFP = 4 L FFP
Effect of FFP on patients with INRs between <1.8 Abdel-Wahab OI, et al. Transfusion 2006; 46: 1279-85
57 trials evaluated Liver disease, cardiac surgery, warfarin-related hemorrhage, massive transfusion, prevention of IVH in infants, burns, etc. …for most clinical situations, the RCT evidence base for the clinical use of FFP is limited…the strongest RCT evidence seems to indicate that the prophylactic use of FFP is not significantly or consistently effective across a range of different clinical settings. Stanworth et al. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials. Br J Haematol. 2004;126:139-52.
Globally there is no evidence… What about for specific procedures?
What is the evidence for specific procedures? Bedside procedures and the evidence: Central venous catheters Liver biopsy Thoracentesis & paracentesis Bronchoscopy & transbronchial biopsy Renal Biopsy Epidural/Lumbar puncture
Central venous catheters 57 year old woman with AML needs a Hickman line insertion to commence chemotherapy today Her INR is 1.9 and PTT 41 this morning – she has suspected mild DIC and vitamin K deficiency (not eating and on broad spectrum antibiotics) Given iv vitamin K 10 mg iv this AM Platelet count is 38 No active bleeding and no bleeding history What would you request?
What do we know? Bleeding complications relate to inadvertant puncture of the carotid or subclavian artery Denys BG, et al. Circulation. 1993;87:1557-62. Vanherweghem JL, et al. Am J Nephrol. 1986;6:339-45. Systematic review of complications of CVC insertion (jugular or subclavian) reported 48 episodes of pneumothorax and/or hemothorax after 3420 procedures (1.4%), although only one-third of the episodes were hemothorax (=0.5% risk of a hemothorax). Ruesch S, et al. Crit Care Med. 2002;30:454-60.
What do we know? A meta-analysis of 8 RCTs found that the use of Doppler ultrasound to guide line placement reduced the incidence of placement complications (OR 0.22, 0.10-0.45) Randolph AG, et al. Crit Care Med. 1996;24:2053-8. Greater experience by the physician performing the CVC insertion reduces the risk of procedural complications Sznajder JI, et al. Arch Intern Med. 1986;146:259-61.
Sunnybrook All our lines are placed with ultrasound guidance by experienced interventional radiologists 0.5% x 0.22 = 0.11% (1 in 909 major bleed rate)
CVC insertion Foster PF, Moore LR, Sankary HN, et al. Central venous catheterization in patients with coagulopathy. Arch Surg. 1992;127:273-5. 202 CVC insertions performed on liver transplant patients with severe hemostatic abnormalities No attempts were made to correct laboratory abnormalities before the procedure Mean coagulation factor levels were 29% of normal (range=10-39%), mean PTT was 92 sec (range=78-100 seconds), mean platelet concentration was 47 (range=8- 79) Despite these values and the lack of any pre-procedure therapy, no serious bleeding complications occurred
CVC insertion Doerfler ME, Kaufman B, Goldenberg AS. Central venous catheter placement in patients with disorders of hemostasis. Chest. 1996;110:185-8. 76 patients who received 104 central catheters 22 catheters were placed with platelet counts of 50-100, 30 catheters with counts of 20-50, and 11 with counts below 20 13 percent of patients had a combination of thrombocytopenia and prolongation of the PT/PTT None were given transfusions of platelets or FFP before the procedure None had serious complications, intrathoracic bleeding, or an unexpected drop in hematocrit
More evidence 115 patients undergoing CVC insertion with thrombocytopenia (mean 24,000/µL) found no difference in the platelet counts of patients with and without bleeding complications. Barrera R, et al. Cancer. 1996; 78:2025-30. 388 consecutive catheterizations in patients with heme malignancies with thrombocytopenia present in 28% of patients (32 patients 50-99, 41 patients 30-49, and 36 patients <30) and abnormal coags were present in 19% Bleeding occurred after line insertion in only 5 cases (1 in 78 patients) and all 5 patients had platelet counts below 30,000/µL. No difference in bleeding rates between patients with normal and abN coags Nosari AM, et al. Leuk Lymph. 2008;49:2148-55.
More evidence Petersen GA. Does systemic anticoagulation increase the risk of internal jugular vein cannulation? (letter) Anesthesiology. 1991;75:1124. 516 consecutive patients with internal jugular lines before cardiac surgery 252 (49%) were anticoagulated with heparin An observer who was unaware of the anticoagulation status of each patient recorded the presence of an insertion site hematoma Of the 22 hematomas that occurred 13 were in anticoagulated patients 9 were in non-anticoagulated persons This difference was not significant
More evidence Fisher NC, et al. Intensive Care Med. 1999;25:481-5. 658 CVC line insertions Median INR was 2.4 (1–16) (580 cases >1.5) Median platelet count was 81 (9 – 1,088) (531 <150) In 453 cases both abnormalities were present Patients were not given any pre-procedure transfusion of FFP or platelets 1patient, with near normal tests, developed a hemothorax after inadvertent puncture of the subclavian artery There were no other major hemorrhagic complications
More evidence Hass B, et al. J Vasc Interv Radiol 2010; 21: 212-217. Of 3188 tunneled CVCs placed: 428 had platelet counts <50 (down to 3) 361 had INR>1.5 (up to 3.8) They excluded any patient that had been transfused product between the last reading and the procedure 3 had bleeding complications None had platelet counts 1.5
Bottom line No evidence for any pre-procedure component therapy Based on the evidence, the most conservation stance you could take would be to require a platelet count in excess of 25-30 There is no INR above which patients appear to be at higher risk
Liver biopsy 45 year old with cryptogenic cirrhosis needs a diagnostic percutaneous liver biopsy (with ultrasound guidance) His INR is 2.2, PTT 48, and platelet count 48 He has no bleeding history What would you order before the procedure?
Liver Biopsy The perfect patient population to test NOT giving prophylactic transfusions: Patients often have abnormal laboratory tests of coagulation They are often thrombocytopenic They have multiple other derangements of hemostasis You cant compress the liver if it bleeds
Piccinino F, Sagnelli E, Pasquale G, et al. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies. J of Heaptology 1986; 2: 165-73. A very large series of 68,276 percutaneous biopsies published in 1986 found that major bleeding occurred in only 42 patients. 1 in 1626 patients
Ewe K. Bleeding after liver biopsy does not correlate with indices of peripheral coagulation. Dig Dis Sci 1981;26:388-93. 200 consecutive patients undergoing liver biopsy with laproscopic observation for bleeding No degree of abnormal lab tests warranted pre- procedure therapy at this institution There was no correlation of liver bleeding time and laboratory test results Even patients with INR>3 and platelets<50 did not bleed more than patients with better test results
McGill DB, et al. A 21-year experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology. 1990;99:1396-400. 9000 liver biopsies performed over a 21 year period Patients had pre-procedure INRs up to 1.8 and platelet counts as low as 55 Post-biopsy hemorrhage occurred in 32 patients The lab values did not differ between the 32 with substantial bleeding and the rest of the patients
Makris M, et al. A prospective investigation of the relationship between hemorrhagic complications of percutaneous needle biopsy of the liver and coagulation screening tests. Br J Haematol. (abstract) 1992;81:51. 104 patients undergoing liver biopsy who were screened for bleeding complications with post- procedure CT scans Half of the patients had abnormal coagulation tests pre-procedure including numerous patients with PT values corresponding to INRs > 2.0, PTTs >50, and platelet counts as low as 50 Two patients bled post-procedure and both of these had normal pre-procedure coagulation values
Bottom line Bleeding is very rare There is no data to support the notion that patients with abnormal lab values will bleed more than patients with normal lab values at the time of percutaneous liver biopsy
Thoracentesis & Paracentesis 67 year old EtOHic male is admitted through the ER with query spontaneous bacterial peritonitis resulting in sepsis INR 5 Platelet count 23 He needs a diagnostic peritoneal tap What would you give him prior to the procedure?
Pache I, and Bilodeau M. Severe hemorrhage following abdominal paracentesis for ascites in patients with liver disease. Ailment Pharmacol Ther. 2005;21:525-9. Severe hemorrhage following abdominal paracentesis is exceptionally rare A recent large series of 4729 patients observing severe hemorrhage in only 0.19% of patients 1 in 525 patients
McVay PA, Toy PT. Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities. Transfusion. 1991;31:164-71. A review of outcomes in 608 consecutive procedures (391 paracenteses, 207 thoracenteses, and 10 both) None of the patients was given prophylactic components Bleeding complications occurred in 0.2% No difference between normal PT/PTT compared with those with a prolonged PT/PTT No differences between platelet counts above 100 compared with those with counts of 50-100 or 25-50
Grabau CM, et al. Performance standards for therapeutic abdominal paracentesis. Hepatology. 2004;40:484-8. 1,100 paracenteses at a center where no degree of thrombocytopenia or pre-procedure coagulation test result was deemed unsafe for the procedure All procedures were performed without ultrasound guidance and without the transfusion of platelets or plasma The lowest platelet count was 19 (IQR 42-56) and the highest INR was 8.7 (IQR 1.4-2.2) There was no significant bleeding in any patient
Guidelines In the 2009 American Association for the Study of Liver Diseases Practice Guidelines on the management of adult patients with ascites due to cirrhosis, the guideline committee recommended thatBecause bleeding is sufficiently uncommon, the routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended. Runyon BA. AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49:2087-107.
Transbronchial biopsy 68 year old man on ASA for a bare metal stent placed 1 year ago is booked for bronchoscopy and transbronchial biopsy He has a history of 2 TIAs His platelet count is normal Would you stop his ASA?
Bronchoscopy and Biopsy Complications at the time of bronchoscopy are rare, in one large report a major complication was seen in only 0.08% of 24,521 procedures Complications are higher with transbronchial biopsy, estimated in one large series at approximately 2% for all patients Credle W, Smiddy J, and Gruber B. Deaths and complications of fiberoptic bronchoscopy. Am Rev Respir Dis 1974; 109: 67-72. Cordasco EM Jr, Mehta AC, and Ahmad M. Bronchoscopically induced bleeding. A summary of nine years Cleveland Clinic experience and review of the literature. Chest. 1991;100:1141-7.
Kozak EA, Brath LK. Do screening coagulation tests predict bleeding in patients undergoing fiberoptic bronchoscopy with biopsy? Chest. 1994;106:703-5 274 patients undergoing 305 fiberoptic bronchoscopy and biopsy procedures at a tertiary care institution Prolonged hemostatic studies prior to the procedure were noted in 10% (n=28) of patients 35 patients bled, but 32 of these had normal pre- procedure hemostatic values 3 patients had severe bleeding and each of them had normal pre-procedure test results
Diette GB, Wiener CM, White P Jr. The higher risk of bleeding in lung transplant recipients from bronchoscopy is independent of traditional bleeding risks: results of a prospective cohort study. Chest. 1999;115:397-402 720 bronchoscopies performed over a one-year period at Johns Hopkins and used multivariate analysis to determine factors that correlated with bleeding complications They found that bleeding did not correlate with coagulation parameters or platelet count
Brickey DA, Lawlor DP. Transbronchial biopsy in the presence of profound elevation of the international normalized ratio. Chest 1999;115:1667-71 Transbronchial biopsies on 18 pigs who were treated with escalating doses of warfarin Goal = to determine the INR level at which excess bleeding would occur following the procedure Excess bleeding - > 100 mL in > 50% of animals They had planned to apply different post- procedure therapies to staunch the bleeding But…the warfarin treated animals never developed bleeding despite having INR levels >10 11 of 18 pigs had INR>7 at the time of the biopsy
Herth FJ, Becker HD, Ernst A. Aspirin does not increase bleeding complications after transbronchial biopsy. Chest. 2002;122:1461-4 Effect of aspirin on the extent of bleeding at the time of bronchoscopy and transbronchial lung biopsy 1217 patients - 285 were taking aspirin at the time of the procedure 57 patients (4.7 %) had bleeding complications Incidence of minor (1.8 vs 2.9%), moderate (1.1 vs 1.4%), and severe (0.8 vs 0.9%) bleeding was not statistically different among those taking aspirin and those who did not
Plavix is not Aspirin Ernst A, Eberhardt R, Wahidi M, et al. Effect of routine clopidogrel use on bleeding complications after transbronchial biopsy in humans. Chest. 2006;129:734-7 Prospective observational study Patients undergoing transbronchial biopsy were not required to cease aspirin or clopidogrel before the procedure The post-procedure severe bleeding rate was 28% for clopidogrel alone, 50% for combined use, and 2 of 574 (0.3%) of the control group (of whom 111 were on aspirin alone)
Bottom line There is no strong evidence to support component therapy to protect patients from bleeding complications Although, I feel sympathy for a respirologists nervousness for doing this procedure given the consequences Dont worry about ASA use For transbronchial biopsy, platelet count >25-30 and INR <2 is reasonable compromise Stop oral P2Y 12 -R antagonists
Renal biopsy A 64 year old woman with acute onset of combined hepatic and renal dysfunction is booked for a renal biopsy INR is 1.9 Platelet count is 142 Creatinine in 345 Hemoglobin is 103 Would you give her FFP?
Manno CManno C, et al. Predictors of bleeding complications in percutaneous ultrasound-guided renal biopsy. Kidney Int. 2004;66:1570-7 471 consecutive percutaneous renal biopsies Hematoma seen in 33.3% of patients (clinically silent in 90%) 4 major hematomas observed (0.8%) When patients with and without bleeding complications were compared - no difference in the baseline platelet count or PT The PTT was higher in the patients with these clinically silent hematomas, 102.7% compared to 100.1% (p=0.01), making this finding of questionable importance
Waldo BWaldo B, et al. The value of post-biopsy ultrasound in predicting complications after percutaneous renal biopsy of native kidneys. Nephrol Dial Transplant. 2009;24:2433-9. 162 patients undergoing percutaneous renal biopsy No difference in the PT, aPTT, serum creatinine or hemoglobin at the time of biopsy between patients with (n=26) and without a complication (n=136)
Bottom line No published evidence to support correction of the INR/PTT or platelet count before this procedure
Lumbar puncture 19 year old female with ALL planned for a diagnostic and therapeutic LP (IT MTX) Her platelet count is 38 Her INR is 1.3, PTT 34 Would you transfuse anything prior to the procedure?
Complications are really rare Risk of spinal hematoma following epidural anesthesia - 1 in 280,000 procedures Stafford-Smith M. Can J of Anaesthesiology. 1996; 43:R129-141. The risk of spinal hematoma following lumbar puncture is thought to be lower than that for epidural anesthesia, although reliable estimates are unavailable van Veen JJ, et al. Brit J of Haem 2010;148:15-25
Van Venn JJ, Vora AJ, and Welsh JC. Lumbar puncture in thrombocytopenic patients. Brit J of Haematology 2004; 127: 233-4 Lumbar punctures in 226 children with leukemia Baseline platelet counts were: < 10 in 19 patients 10-20 in 49 20-50 in 89 patients No bleeding complications in any patient
Ruell J et al. Platelet count has no influence on traumatic and bloody lumbar puncture in children undergoing intrathecal chemotherapy. Br J Haematol. 2007;136:347-8 Ruell et al reported no bleeding complications after 738 lumbar punctures in 54 children with leukemia with platelet counts between 30 and >90 In addition, there was no correlation between the platelet count and the incidence of bloody taps
Howard SC, et al. Safety of lumbar puncture for children with acute lymphoblastic leukemia and thrombocytopenia. JAMA. 2000;284:2222-4. Howard SC, et al. Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia. JAMA. 2002;288:2001-7. 5,000 lumbar punctures in 958 consecutive children with leukemia 170 done in patients with counts between 10-20 742 done in patients with counts between 20–50 858 done in patients with counts between 50–100 Platelet transfusions were not given prior to the LP No patient developed spinal hematoma or a clinical bleeding complication
Bottom line There is no evidence that patients with platelet counts between 10-100 have a higher risk of complications than patients with higher platelet counts
What about regional anesthesia? No complications in 170 patients undergoing regional anesthesia with counts between 50-100 Frenk V, Camann W and Shankar KB. Regional anesthesia in parturients with low platelet counts. Can JAnaesth. 2005;52,114. No complications in 65 patients of 10,369 births undergoing regional anesthesia with counts <150 (only 9 patients had counts<100) Bernstein K, Baer A, Pollack M, et al. Retrospective audit of outcome of regional anesthesia for delivery in women with thrombocytopenia. J Perin Med. 2008;36,120–3. No complications in 25 patients of 10,203 births undergoing regional anesthesia with platelet counts <100 Deruddre S, Peyrouset O and Benhamou D. [Anesthetic management of 52 deliveries in parturients with idiopathic thrombocytopenic purpura]. J Gynecol Obstet Biol Reprod (Paris). 2007;36,384–8.
van Veen JJ, et al. The risk of spinal haematoma following neuraxial anesthesia or lumbar puncture in thrombocytopenic individuals. Brit J of Haematol. 2010;148:15-25 In a superb review of the risks of spinal hematoma following regional anesthesia, the authors conclude that there is sufficient literature to conclude that a platelet count >80 is sufficient for an epidural or spinal anesthesia They also state that it is likely that it is safe to perform this procedure at lower platelet counts but at this time there is insufficient literature to recommend a lower level
Summary Bleeding complications at the time of a procedure are exceptionally rare Mildly abnormal test results do not imply clinically abnormal clotting (coagulopathy) Platelet reserve is likely MORE important than deficits in coagulation factors It is time to switch to a therapeutic mode (not prophylactic) – only treat bleeding when it happens If you are very conservative and nervous clinician PLT 25 and INR 2