© 2018 Kurt Pfeifer.

HEMATOLOGIC DISEASE

ASSESSMENT

Data Gathering

History

Symptoms

  • Previous evaluation for anemia, bleeding disorder or thrombophilia

  • Previous thromboembolism

  • Bleeding with invasive procedures

  • Family history of easy bruising, bleeding, anemia, or thromboembolism

  • Frequent infections

  • Spontaneous bleeding (epistaxis, hematochezia, hematuria, hematemesis, melena)

  • Heavy menses

  • Fatigue

  • Easy bruising

  • Peripheral edema

Exam

  • Ecchymoses/petechiae on skin or mucosa

  • Pallor

Risk Stratification

Diagnostic Studies

Anemia/Polycythemia

Leukopenia

Thrombophilia

  • SCREENING: obtain CBC for any of following:

    • Expected total blood loss >1000 cc​

    • History or exam suggestive of RBC abnormality

  • ANEMIA: obtain following if not obtained recently (<6 months)​:

    • CBC, reticulo​cyte count, iron panel, ferritin, B12, TSH

  • POLYCYTHEMIA:​ obtain following if not previously evaluated:

    • EPO​

  • Obtain CBC with differential for any of following:

    • Myeloproliferative disease

    • Recurrent or suspected current infection

    • Known leukopenia

    • Liver disease

  • Evaluation generally not indicated purely for perioperative purposes - treat as high-risk for VTE if history or exam suggests hereditary or acquired thrombophilia

Bleeding Risk

  • SCREENING:  if craniotomy or history/exam suggestive of bleeding disorder, obtain platelet count, INR, PTT, and platelet aggregation testing (e.g., PFA-100)​. 

  • KNOWN BLEEDING DISORDERS: see Management section

  • ABNORMAL SCREENING STUDIES: follow figures below

Isolated PTT Elevation

MANAGEMENT

Indications for Surgical Delay

  • VTE within 3 months, especially within 1 month (forthcoming SPAQI guideline)

  • Uncharacterized or untreated correctable anemia (Hgb <10 or any anemia prior to large blood loss surgery) & elective surgery (Choosing Wisely)

  • Thrombocytopenia that is new/significant (<50k or decrease by 50% with platelet count <150k or related to microangiopathic hemolytic anemia (DIC, TTP, HUS)

  • Severe neutropenia (ANC <500)

Medication Management

  • Continue all non-antithrombotic hematologic meds uninterrupted (eg, hydroxyurea)

    • Exceptions: rituximab - discuss best management with surgeon and hematologist

Chronic Anticoagulation

RAPID REVERSAL FOR URGENT SURGERY

  • WARFARIN:

  • DOACs:​

    • If patient not bleeding, costs and thrombotic risks of reversal may outweigh benefits​ - discuss with surgeon, anesthesiology, and hematology

    • Dabigatran: idarucizumab 5 g IV bolus

    • Oral Xa inhibitors (rivaroxaban, apixaban): andexanet IV bolus and 2-hour infusion (only FDA-approved for reversal of anticoagulation in life-threatening bleeding)

BRIDGING

  1. Determine if anticoagulation interruption is required (ACC Expert Consensus Pathway)

    • If no bleeding risk factors plus low bleeding risk surgery & on warfarin or very low​ bleeding risk surgery & on DOAC, do not interrupt anticoagulation

      • Bleeding Risk Factors:

        • Major bleed or ICH within 3 mo

        • Thrombocytopenia

        • Platelet dysfunction (including antiplatelet use)

        • Supratherapeutic INR

        • Bleeding with previous bridging or similar procedure

      • Low Bleeding Risk Procedures:​

        • Very Low: Cataract, Arthrocentesis

        • Low: Carpal tunnel release, Hysteroscopy, Ureteroscopy, CIED placement

  2. Determine if bridging anticoagulation required if anticoagulation interrupted - indications:

    • WARFARIN:

      • Do not provide bridging for patients on chronic anticoagulation for previous VTE but are at low or moderate risk for VTE recurrence (ASH guideline)​​

      • Consider briding for patients at high risk for VTE recurrence if no bleeding risk factors (ACCP perioperative guideline):

        • Severe thrombophilia (eg, deficiency of protein C, protein S, or antithrombin; antiphospholipid antibodies; multiple abnormalities)

        • VTE within 3 months

          • Consider placement of retrievable IVC filter for surgery if surgery required within 1 month of VTE and has risk factors for morbidity/progression/recurrence​ (forthcoming SPAQI guideline):

            • Positive D-dimer; extensive thrombosis (e.g., >5 cm in length, involves multiple veins, >7 mm in maximum diameter); thrombosis close to the proximal veins; no reversible provoking factor for DVT; active cancer; prior VTE; inpatient status​ (extrapolate from ACCP VTE management guideline recommendations for subsegmental PE)

    • DOACs: DO NOT BRIDGE (stop and restart medication per instructions in Medication Management) (ACC Expert Consensus Pathway)

  3. If bridging required, follow this protocol:

    • Last dose of warfarin 5 days before surgery​ if INR 2-3 (3-4 days before if INR <2 and ≥5 days if INR >3) 

    • Start LMWH 1 mg/kg or therapeutic IV UFH once INR subtherapeutic (36-48 hours after last warfarin dose)

    • Provide last dose of therapeutic LMWH 24 hours before surgery and neuraxial/regional anesthesia; stop UFH 4-6 hours before surgery and neuraxial/regional anesthesia

    • Resume warfarin 12-24 hours after surgery

    • Resume therapeutic LMWH/UFH no early than 24 hours after low bleeding risk surgery and 48-72 hours after non-low bleeding risk surgery (always confirm with surgeon before resumption)

Venous Thromboembolism (VTE) Prophylaxis

  • For all surgeries other than orthopedic, neurosurgery, and cardiothoracic, compute the Caprini score

  • For orthopedic, neurosurgery, and cardiothoracic, assess for risk factors for VTE which may prompt more aggressive prophylaxis than typically provided:

    • Previous VTE​

    • Strong family history of VTE (>1 1st degree relative)

    • Oral estrogen or tamoxifen use

    • Active cancer

  • For total knee or hip arthroplasty, assess for contraindications for aspirin use: recent peptic ulcer disease or previous gastric bypass surgery​

Transfusion Management

RBC Transfusion Indications (AABB guideline)

  • Symptoms of anemia (along with level of anemia expected to cause symptoms - eg, Hgb <10 and significantly decreased from baseline)

  • Hgb <7 g/dl

  • Hgb <7.5 after cardiac surgery (2018 PBM International Consensus Conf)

  • Hgb <8 g/dl plus:

    • Cardiovascular disease​

    • Orthopedic surgery

Platelet Transfusion Indications (AABB guideline)

  • Platelet count <10,000/mm3

  • Platelet count <20,000/mm3 and undergoing central venous access device placement

  • Platelet count <50,000/mm3 and undergoing non-neuraxial surgery or lumbar puncture

  • Platelet count <100,000/mm3 and undergoing intracranial or cardiac surgery

Blood Conservation Methods (BCSH guideline​, SABM recommendations)

Iron Supplementation

  • In patients with preoperative iron deficiency anemia, IV iron reduces blood transfusions & is indicated when the timeframe to surgery is short (few weeks) or the patient is intolerant of PO iron (Froessler et al & Goodnough et al)

  • Even in patients without preoperative anemia, provision of postoperative IV iron after lower limb arthroplasty reduced transfusion rates without significant change in overall cost of care (Munoz et al)

IV iron.jpg

Preoperative Autologous Donation 

  • Low use currently due to less concern over safety of blood supply & evidence suggesting it may increase the need for transfusion (due to donating blood close enough to surgery to prevent blood expiration) and does not completely eliminate risks

  • If used, iron supplementation and ESAs may be beneficial for regenerating blood after donation and prior to surgery (see above)

  • BCSH guideline only recommends its use in "exceptional circumstances":

    • Rare blood groups or multiple blood group antibodies where compatible allogeneic (donor) blood is difficult to obtain

    • Serious psychiatric risk because of anxiety about exposure to donor blood

    • Refusal of allogeneic blood transfusion but will accept preoperatively donated autologous blood

    • Children undergoing scoliosis surgery

RBC Salvage

  • Can be done intraoperatively or postoperatively (less common)

  • Used if expected blood loss >500 cc

  • Indications:

    • Expected blood loss >20% of patient’s blood volume

    • Risk factors for bleeding (including high-risk Caesarean section) or low preoperative Hb concentration 

    • Major hemorrhage

    • Rare blood groups or multiple blood group antibodies

    • Refusal of allogeneic blood transfusion but will accept salvage autologous blood (many Jehovah's Witnesses, but not all - see below)

Acute Normovolemic Hemodilution (ANH)

  • Immediate preoperative phlebotomy and storage of RBCs and replacement with isotonic IV fluids

  • Requires considerable expertise & resources not available at all facilities

  • Role still unclear

  • Consider for anemic patients undergoing surgery who refuse allogeneic blood or with large expected blood loss who have rare blood groups or multiple RBC antibodies that make allogeneic transfusion difficult

Erythropoiesis-Stimulating Agents

  • Beneficial in patients with anemia of chronic disease prior to large blood loss surgeries

  • Potential adverse effects: VTE, seizures, red cell aplasia

  • Contraindication: Hct >35%

  • Should be given with concomitant iron supplementation & VTE prophylaxis should be considered

  • Preparations contain a small amount of human albumin so some Jehovah's Witnesses may not accept

ESAs.jpg

Sickle Cell Disease Management

  • Transfuse to Hgb of 10 g/dl prior to surgery requiring general anesthesia (NHLBI guideline)

    • Type of transfusion (simple or exchange) should be determined by hematology​

    • Typically done 2-3 days before surgery

  • Provide additional time for crossmatching of blood prior to large blood loss surgeries​ - 2 days before surgery

  • Aggressively pursue adequate pain control & avoidance of hypoxia/dehydration

  • If patient is euvolemic, give hypotonic IV fluids (encourages flow of water into RBCs and prevents sickling)

Jehovah's Witness Patient Management (Kline et al)

  • Obtain advance directives (Jehovah's Witnesses often have a unique advance directive)

  • Some patients may request additional assistance from Jehovah's Witness pastors or councils - many Hospital Liaison Committees available (click for website with list)

  • Confirm whether they will take direct transfusion of blood cells

    • Strict adherents ("active" Jehovah's Witnesses) will not​ accept primary blood components - RBCs, platelets, WBCs, and plasma

    • "Inactive" Witnesses may be willing to receive blood transfusions under some circumstances

  • Blood derivatives, including albumin, cryoprecipitate, immunoglobulins, and factor concentrates, are left to individuals to decide (governing body for Jehovah's Witnesses, the Watch Tower Society, leaves it to one's conscience)

  • Ask whether they will accept specific blood conservation methods (see above)

    • Many will accept RBC salvage and ESAs

    • For RBC salvage, many insist that the blood is not stored at any time - instead, it must be in a continuous circuit connected to the body; not all RBC salvage methods do this - must determine ahead of time

    • For ESAs, all usually contain a small amount of albumin; for Jehovah's Witnesses unwilling to accept this, albumin-free preparations can be obtained from the manufacturer

  • Obtain CBC, iron studies, B12, folate, coagulation studies, & fibrinogen levels

  • At least 6 weeks before elective surgery likely to be associated with significant blood loss, check Hb and if <13, optimization by treatment with iron and/or erythropoietin should be considered

  • Minimize phlebotomy

  • Use antithrombotic agents cautiously

  • Consider use of IV tranexamic acid to reduce bleeding/conserve blood

Von Willebrand Disease (vWD) (ASH vWD pocket guide)

  • Obtain specific perioperative management plan from hematology

  • DDAVP may only be used for minor procedures in type 1 vWD

    • Based on prior response to test dose

    • 0.3 mcg/kg IV or 300 mcg intranasally 30 min before procedure

    • May redose q12-24 hrs depending on bleeding risk

    • Tachyphylaxis occurs after >3 doses

    • Decrease water intake and monitor for hyponatremia and volume overload

  • Provide von Willebrand factor (vWF) concentrates for all other situations and types of vWD

    • Most products are “impure” factor VIII concentrates that contain vWF in all multimers (e.g., Humate-P ©)

    • Dose: 30-60 units/kg IV 1 hr prior to surgery and repeated q12-24 hrs to maintain target vWF level

    • Minor surgery: vWF level >30 units/dl for 3-5 days postop

    • Major surgery: vWF level >50 units/dl for 7-14 days postop

Hemophilia

  • Obtain specific perioperative management plan from hematology

  • Provide factor VIII or IX as needed to maintain factor activity level 75-100% for 3 days after surgery and then 50% until healing complete

    • Need info on patient’s factor VIII/IX response (what dose achieved 75-100% level) & if they have known factor inhibitors

    • Requires dosing/factor level measurement 1 hour prior to surgery and q8-12 hours initially

    • Since therapy needed for prolonged period of time, consider placement of PICC​

  • Usually require postop admission, even for minor surgeries

Other Bleeding Disorders

  • Obtain specific perioperative management plan from hematology

  • Often require postop admission, even for minor surgeries

COMMUNICATION/COUNSELING

  • Collaborate with patient's hematologists

  • For patients with bleeding disorders requiring blood products (vWD, hemophilia, and others) provide advance notice to blood bank of pending surgery and likely product needs since these may not be kept in stock in the amounts required