Hematologic disorders are diseases of circulating blood cells and plasma proteins that play a role in oxygen delivery, inflammation, infection control, hemostasis, and thrombosis. Given that surgery can result in bleeding and induce hemostatic changes that promote thrombosis, it is not surprising that patients with hematologic disorders present serious preoperative management challenges. The ability of hospitalists to manage diseases associated with blood disorders, and hemostatic and thrombotic risks associated with surgery is vital to the welfare of these patients. This chapter will discuss preoperative assessment of patients with hematologic disorders, and review the risk of perioperative hematologic complications and specific management strategies to reduce perioperative risks in this vulnerable patient population.
PREOPERATIVE ASSESSMENT OF PATIENTS WITH HEMATOLOGIC DISORDERS
HISTORY AND PHYSICAL EXAMINATION
The most important aspect in the preoperative assessment of patients with a hematologic disorder is a thorough history. This is especially true for patients with hemostatic disorders (Table 54-1). Though the patient may have a known hemostatic diagnosis, the clinical phenotype of these patients may vary considerably. Occasionally, a patient may report an unexpected personal and/or family history of bleeding or thrombosis, or a hematologic diagnosis as a child with no subsequent follow-up. Depending on the severity of the presumed diagnosis, these subjective accounts may need to be confirmed objectively. The physical examination is rarely helpful in such situations. However, the presence of petechiae, purpura, ecchymoses, jaundice, ascites, and splenomegaly may alert one to the presence of potential hematologic disorder.
TABLE 54-1Recommended Questions to Ask in Patients with Known or Suspected Hemostatic Disorders ||Download (.pdf) TABLE 54-1 Recommended Questions to Ask in Patients with Known or Suspected Hemostatic Disorders
Have you or anyone in your family ever been labeled a “bleeder”? Has someone in the family ever experienced abnormal bleeding?
Have you ever bled with surgery or following childbirth? What surgical procedures have you had, including major surgery, minor surgery, biopsies, and dental extractions?
Did a surgeon or dentist ever have to re-explore the wound site or did you ever have to return to the operative suite for hemorrhagic control?
Have you ever had excessive menstrual periods? How long do your periods last? How many pads or tampons are needed each day? Have you ever required iron supplementation for anemia due to a menstrual blood loss?
Do you bruise excessively? Are these bruises multiple? Are they confined only to the outer thighs or other areas that are subject to trauma? Are any of these bruises palpable (ie, are they true hematomas) or are they level with the surface of the skin?
Do you have nosebleeds now or was there ever a time in your life when you did have spontaneous nosebleeds?
Have you ever required a blood or plasma transfusion and, if so, why?
Have you ever bruised or experienced hemorrhage following trauma, car accidents, falls, organized or unorganized sports, altercations, or any acts of violence?
Similarly, given the high perioperative complications in patients with sickle cell disease (SCD), a careful history is critical to ensure optimal surgical outcomes. Specific questions include recent cough, wheezing, dyspnea on exertion, fever, ankle edema, right upper quadrant pain, change in stool or urine color, hematuria, or dysuria. In addition, details on past SCD-related complications should be documented, including acute chest syndrome, frequency of pain episodes, strokes, hyperhemolytic crisis, pulmonary hypertension, aplastic crisis, transfusion reactions, and alloimmunization.
In addition to the specific questions above, all patients with hematologic disorders should have the following documented: alcohol use, smoking history, past anesthesia history, current medications (including vitamins, supplements, and herbal preparations), and allergies. Herbal remedies are often self-administered by patients and can modify hemostasis. These medications should be stopped prior to surgery.
It has been established by multiple prospective studies that the use of routine preoperative coagulation testing is not helpful in the absence of a bleeding history. In contrast, a preoperative complete blood count and coagulation testing is essential in patients with known hematologic disorders. Table 54-2 list laboratory and radiology studies that should be considered in the preoperative assessment of these patients.
TABLE 54-2Laboratory and Radiology Studies ||Download (.pdf) TABLE 54-2 Laboratory and Radiology Studies
All patients with hematologic disorders
Platelet function tests
von Willebrand antigen and ristocetin cofactor
Factor assay (eg, factor V, factor VIII, factor IX, factor XI, factor XII)
Peripheral blood smear
Iron studies and ferritin
Vitamin B12 and folate levels
Lactate dehydrogenase (LDH)
Sickle cell disease
PERIOPERATIVE RISK ASSESSMENT AND MANAGEMENT FOR HEMATOLOGIC DISORDERS
Patients with hematologic disorders are at increased risk for complications related to changes in blood cells and plasma factors initiated by surgery. The magnitude of the risk may vary considerably with the underlying hematologic disorder, nature of the surgery, age of the patient and other comorbidities. These disorders may require specific treatment and consultation with hematologists to ensure an accurate assessment of risk of perioperative complications and to improve outcomes. This involves understanding the nature and severity of the hematologic disorders with the goal to minimize the risk of intraoperative bleeding and postoperative complications including bleeding, infection, thrombosis, and abnormal wound healing. This section discusses several common hematologic disorders that hospitalists may encounter, the nature of the perioperative risk and specific perioperative management.
DISORDERS OF RED BLOOD CELLS
Anemia is a very common abnormality in patients undergoing surgery and is even more common in patients with active hematologic disorders due to treatment, marrow involvement by the disease, bleeding, renal failure, inflammation, or advanced age. Adequate red cell mass is needed to promote tissue oxygen delivery and is a vital factor to aide wound healing and prevent myocardial and central nervous system injury in surgical patients. Red cells can also promote hemostasis and play an important role in postoperative recovery.
Given the importance of red cells, the presence of anemia needs to be recognized preoperatively and corrected if surgery is not emergent. Previously, transfusion of red cells was considered a desirable intervention. However, the administration of red cells was discovered to adversely affect the morbidity and mortality of hospitalized patients in a wide variety of clinical settings. Preoperative anemia has to some extent been a silent risk factor for adverse clinical outcomes due to unnecessary transfusion of red cells that can increase perioperative complications. On the other hand, excess number of red cells may cause hyperviscosity and lead to thrombosis. For instance, patients with polycythemia may need preoperative phlebotomy to reduce the risk, especially when it is caused by polycythemia vera. Common hematologic disorders that can cause anemia and polycythemia will be reviewed.
Patients with iron deficiency anemia should have their anemia corrected preoperatively with oral iron if there is sufficient time, or with intravenous iron if a more urgent response is required. The cause of iron malabsorption or loss should be identified and any possible source of bleeding identified. Folic acid and vitamin B12 are nutrients required to promote proliferation of marrow cells to produce red cells, as well as white cells and platelets. Once these nutrients are replete, it may take several days to start to see a reticulocyte response and several weeks to restore the blood count to normal.
More commonly, some patients do not have a single factor contributing to anemia and correction is often difficult due to diseases associated with renal insufficiency and chronic inflammation that can adversely affect iron utilization, resulting in reduced red cell production. In such circumstances, red cell transfusion may be required to maintain adequate tissue oxygen delivery during surgery.
Anemia due to production of IgG or IgM autoantibodies is challenging and may require pre- and postoperative interventions. Patients with autoimmune-mediated hemolytic anemia (AIHA) usually have positive Coombs tests, with pan-agglutination of their plasma with donor red cells. The presence of warm IgG autoantibodies results in hemolysis of both the native and transfused red cells making it difficult to provide “crossmatch” compatible blood for surgery. Despite this, when medically necessary, serologically incompatible but type-specific red cells should be transfused if the patient’s hemoglobin levels are causing hypotension and organ dysfunction. Acutely decompensating patients with AIHA who received serologically incompatible blood transfusion do not experience transfusion-related alloimmunization or an increase in hemolysis. Thus, life-saving red cell transfusion should not be denied due to serologically incompatible blood.
Patients with cold agglutinin disease produce IgM antibodies that react in the cold and fix complement to the red cells, promoting extravascular clearance by the reticuloendothelial system. Cold agglutinin disease can occur in response to mycoplasma infection, autoimmune disease and in lymphoproliferative disorders, such as Waldenstrom’s macroglobulinemia. These antibodies can be detected with a positive Coombs test that is complement-mediated. Blood transfusion in patients with cold agglutinin disease should be infused via a blood warmer. If the antibodies are actively promoting hemolysis at room temperature, the patient should be kept warm to prevent hemolysis by increasing the room thermostat.
Many patients with antibody-mediated hemolytic anemia may have had a surgical splenectomy as treatment for their hematologic disorder. Splenectomized patients are at increased risk for both bacterial infection and thromboembolism, both of which can affect perioperative morbidity and mortality. All splenectomized patients should receive immunization against the following organisms: Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis. These vaccinations should be given at least 14 days prior to elective splenectomy or immediately after an emergent splenectomy. In addition, splenectomized patients are at increased risk for venous thromboembolism (VTE) and should receive adequate VTE prophylaxis in the immediate postoperative period.
Patients with atypical hemolytic-uremic syndrome (aHUS) or paroxysmal nocturnal hemoglobinuria (PNH) experience hemolysis due to defects in complement regulation. These patients may be receiving treatment with the complement inhibitor, eculizumab. Since this drug inhibits complement activation, a major mechanism to fight infection, these patients are prone to meningococcemia. A raised awareness of the possibility of meningococcal infection is warranted in these patients.
Patients with hemolytic disorders should receive folic acid, vitamin B12 and iron supplementation to promote hemoglobin synthesis and red cell production. These nutrients should be replete prior to any elective surgery. Patients with coexisting renal failure or chronic inflammation may not produce adequate erythropoietin to promote accelerated erythropoiesis in response to anemia. These patients typically have red cell half-lives that are reduced at least 8-fold and require reticulocyte levels >10% to maintain normal levels of red blood cells. Exogenous erythropoietin injections may be required to compensate for the shortened red cell survival.
Sickle cell disease and other hemoglobinopathies
There exists a substantial degree of variability in the clinical severity of all molecular forms of sickle cell disease. This is due to a wide variety of abnormalities in the hemoglobin molecule. The most common form of sickle cell disease is due to a homozygous point mutation in the beta chain of hemoglobin that leads to the intracellular polymerization of soluble hemoglobin. The cells undergo a change in their shape and forms cells that can be seen on blood smears as irreversible sickle cells. Sickle cell disease presents major challenges to the hospitalist during the pre- and perioperative care.
There can be variable degrees of anemia and end organ damage in sickle cell disease. Some patients experience mild anemia and limited pain crisis while others can have severe hemolytic anemia complicated by pulmonary hypertension, liver disease, renal insufficiency and osteonecrosis of hip and other bones. Strategies for risk reduction require a multidisciplinary approach with surgery, anesthesia and medicine developing a customized care plan for the patient based on surgical risk and severity of sickle cell disease. During the perioperative period, patients with sickle cell disease are at increased risk of painful crisis, acute chest syndrome, and cerebrovascular accidents as surgical procedures may be complicated by hypoxia, hypothermia or acidosis; all of which promotes red cell sickling. The surgical and anesthesia team need to pay special attention to perioperative hydration, oxygenation status and underlying pulmonary, and cardiovascular disease. If the surgery involves general anesthesia, it is strongly recommended that red blood cells be transfused (either through simple or exchange transfusion) in patients with sickle cell anemia (Hb SS) to bring the hemoglobin level to 10 g/dL as this has been shown to reduce perioperative mortality and complications. In patients who already have a hemoglobin level higher than 8.5 g/dL without transfusion, are on chronic hydroxyurea therapy or require high-risk surgery (eg, neurosurgery, prolonged anesthesia, cardiac bypass), a hematologist with experience in sickle cell disease management should be consulted for guidance on appropriate transfusion methods.
As these patients are at high-risk for red blood cell (RBC) alloimmunization, a presurgery type and screen is sent to Blood Bank ahead of time to identify and characterize RBC antibodies (if any), which can be a laborious effort. If no antibodies are found, typically leukocyte-reduced RBC units, which are phenotypically matched for C, E, and Kell as well as ABO and D antigens, are transfused. If antibodies are present, finding compatible phenotypically match units can be time-consuming, hence the need to plan ahead.
Postoperatively, if the patient has a history of acute chest syndrome, admission to the intensive care unit should be considered for close respiratory monitoring. Regardless of location, the primary team should pay particular attention to hydration and oxygenation status. Dehydration and low oxygen levels can precipitate erythrocyte sickling, leading to vaso-occlusive crisis. For management of postoperative surgical pain, patients with chronic pain may have opioid tolerance and require higher doses of narcotics. Reports of pain should be treated accordingly and narcotics should not be withheld for fear of addiction as stress from acute pain can trigger the onset of a vaso-occlusive crisis. On the other hand, overhydration and excessive narcotic use can lead to pulmonary edema and respiratory depression, respectively. Hence, these patients require strict monitoring of hydration and oxygenation status. An incentive spirometer should be prescribed to all patients with sickle cell disease postoperatively as this has been shown to reduce pulmonary complications. Patients with sickle cell disease are also at increased risk of venous thromboembolism (VTE). Given that surgery is a known transient risk factor for VTE, appropriate VTE prophylaxis (either mechanical and/or pharmacological) should be prescribed.
Hemolytic anemia can also occur due to metabolic defects in red cells. Red cell membrane proteins are prone to oxidative damage. The red cells must be capable of reducing oxidatively damaged cells or they will be removed from the body, resulting in hemolysis. Glucose-6-phoshate dehydrogenase deficiency is a common X-linked metabolic disorder that can lead to hemolytic anemia. Patients with this disorder are usually well compensated but will become symptomatic when exposed to drugs that lead to oxidative stress. These patients must not be exposed to specific drugs that can lead to a major hemolytic crisis. The list of drugs that causes hemolysis is published online at: http://g6pd.org/en/G6PDDeficiency/SafeUnsafe/DaEvitare_ISS-it and should be reviewed to minimize the hemolytic risk to these patients preoperatively.
DISORDERS OF STEM CELLS: MYELODYSPLASTIC SYNDROME AND MYELOPROLIFERATIVE DISORDERS
There are several hematologic disorders that can alter white blood cell counts and qualitative function that may lead to serious complication for patients should they require surgical intervention. There are a growing number of individuals over 60 years of age with myelodysplastic syndrome (MDS). This disease syndrome represents a wide variety of defects in the bone marrow stem cells that can cause abnormalities in the production of red cells, white cells and/or platelets. These patients may have varying degrees of blood cell production abnormalities and be at risk for bleeding, infection or thrombosis and cardiopulmonary compromise due to anemia. They may require support with red cells because they are severely anemic and have a low reticulocyte count. Some patients with MDS are responsive to exogenous erythropoietin but others require transfusion support. The hematologist caring for these patients should assist in providing guidance regarding marrow function.
In patients with myeloproliferative disorders, such as polycythemia vera (PV) and essential thrombocythemia (ET), there is an increased perioperative thrombohemorrhagic risk. A high proportion of these surgeries are complicated by vascular occlusion or by major hemorrhage. Uncontrolled PV leads to marked increase in blood viscosity and stasis, reduced capillary blood flow, and subsequently tissue hypoxia. The risk of cardiovascular death and major thrombosis is reduced in patients with PV when the hematocrit is maintained at less than 45% with the use of phlebotomy, with or without cytotoxic chemotherapy. However, it is unclear if an acute reduction in hematocrit results in a decrease in perioperative thrombohemorrhagic risk. A large retrospective study of patients with myeloproliferative disorders undergoing surgery found that despite adequate control of blood count with phlebotomy and administration of standard VTE prophylaxis, these patients had increased bleeding risk (7.3%) and high rates of symptomatic VTE (7.7%) after surgery.
In patients with ET, the uncontrolled production of platelets and megakaryocyte proliferation can often lead to a dramatic increase in platelet count over one million. Platelet function may also be abnormal with defects in both adhesion and/or aggregation responses. The bleeding risk seen in patients with ET can be attributable to either dysfunctional platelets or acquired von Willebrand disease. Patients with acquired von Willebrand disease and ET are more likely to suffer from hemorrhagic events than thrombotic events. The risk of both thrombosis and hemorrhage is higher in older patients and in those who have had prior events. Lowering of hematocrit and platelet count should ideally be done over several weeks to months. Elective surgery should be delayed to allow the hematologist to treat the elevated platelet count or increased red cell mass. If surgery is imminent, repetitive phlebotomy in PV patients to lower the red cell count or platelet pheresis to rapidly lower platelet count in ET are also therapeutic options.
DISORDERS OF WHITE BLOOD CELLS: BENIGN AND HEMATOLOGIC MALIGNANCIES
Hospitalists sometimes encounter a patient that has a low neutrophil count but is not symptomatic and no history of recurrent infections. Benign ethnic neutropenia is due to a polymorphism seen in several ethnic groups of African and Middle East descent. These patients usually do not have an increased risk of infection and no specific intervention is required perioperatively. In contrast, patients with severe congenital neutropenia are prone to infections and have a much lower absolute neutrophil count, usually <500/mm3. About half of all cases of severe congenital neutropenia are caused by mutations in the ELANE gene. These patients may require granulocyte-colony stimulating factor (G-CSF), which increases the neutrophil count and decreases the severity and frequency of infections.
Patients with acute hematologic malignancies (acute myeloid or lymphocytic leukemia) are often anemic, leukopenic and/or thrombocytopenic. They are at a high perioperative risk for bleeding and infection risk. These cytopenias can occur as a clinical manifestation of the underlying hematologic disorder or from bone marrow suppression from treatment with antineoplastic agents. If a patient receiving treatment for a hematologic malignancy requires surgery, the cytopenias secondary to antineoplastic agents or radiation therapy usually recovers 14 to 21 days after exposure to these marrow suppressive agents. It may be prudent to delay elective surgery to allow for bone marrow recovery to minimize both bleeding and infection risk. If surgery is imminent, red cells and platelet transfusion may be required along with aggressive antimicrobial therapy. The use of G-CSF may also be considered to promote leukocyte recovery.
In addition, these patients are often deconditioned with poor functional status from the effects of chemotherapy and prolonged hospitalization, placing them at higher risk for postoperative complications. Antineoplastic agents can also result in poor wound healing. Postoperatively, careful attention should be paid to their nutritional status and rehabilitation to minimize these risks.
DISORDERS OF PLATELETS: CONGENITAL PLATELET DISORDERS AND THROMBOCYTOPENIA
For patients with congenital platelet disorders with a known bleeding history, transfusion of single-donor platelets is usually recommended prior to surgery. The most common platelet disorder is storage pool disease, but there are several other abnormalities that affect platelet aggregation. Postoperatively, depending on the type of surgery, additional platelet transfusion maybe recommended prophylactically or if clinically indicated to manage postoperative bleeding. In patients in whom platelet transfusion is ineffective due to alloantibody development, recombinant factor VIIa (rFVII) has also been used with some success. In certain individuals with mild bleeding phenotype, the consulting hematologist may recommend the use of desmopressin (DDAVP). This is given daily or twice daily for about 3 days before it becomes ineffective due to tachyphylaxis. DDAVP is known to cause fluid retention leading to hyponatremia, thus strict fluid balance is required to avoid electrolyte imbalances postsurgery.
Another common acquired hemostatic disorder is thrombocytopenia, which can be due to decreased production (eg, bone marrow suppression from hematologic malignancies) or increased platelet destruction (eg, immune thrombocytopenia). With the availability of platelet transfusion, even high-risk surgeries can be performed in the severely thrombocytopenic patients. A platelet count of >100,000/μL is usually adequate for all surgical procedures, including high-risk procedures (eg, neurosurgical or spinal surgery). For low- to moderate-risk surgical procedures, transfusion to increase the platelet count to >50,000/μL is usually recommended. Serial monitoring of the platelet count is important during the postoperative period as platelet survival is usually shortened and additional platelet support may be needed. In cases of coexisting liver disease due to cirrhosis or other disease process, the patient may have an enlarged spleen that will sequester platelets, resulting in variable degrees of thrombocytopenia. Furthermore, patients with hepatitis C and cirrhosis may have low thrombopoietin (TPO) levels. These patients may respond to TPO-mimetic agents (romiplostim and eltrombopag) and can be treated for a short duration if needed to optimize management. There is a thrombotic risk with the use of TPO-mimetic agents and this treatment should only be considered when other approaches have failed and bleeding risk is high.
In patients with immune thrombocytopenia (ITP), prophylactic platelet transfusion prior to surgery is usually ineffective. Instead, glucocorticoids and/or intravenous γ-globulin are prescribed to increase the platelet count. Since prednisone and other glucocorticoids can interfere with wound healing, other regimens are preferred in the patient that needs surgery. Other options include RhoGAM (anti-Rh therapy if the patient is Rh antigen positive) and TPO-mimetic agents to increase the platelet count. This can take several days to weeks to observe a response.
Patients with inherited disorders of coagulation (eg, hemophilia A, hemophilia B) are at increased risk of intra and postoperative bleeding. These patients often have an established outpatient hematologist that can define the severity of the patient’s disease and risk for bleeding. The risk should not be underestimated as bleeding into deep tissues, vital organs or along tissue planes can lead to severe hypotension, organ damage and death. A wide variety of hemostatic agents are available to reduce bleeding risk. Issues that assist in defining the dose of hemostatic agent depend upon baseline clotting factor level, nature of surgery and prior clinical response to treatments.
Specific guidelines have been published for management of defects in coagulation factors. All patients should have a treatment plan defining the nature of the product to be used to correct the defect, how the treatment should be monitored and the duration of therapy. Elective surgery should not be performed at an institution that does not have the availability to monitor and infuse the recommended coagulation factor replacement. Perioperative recommendations should be detailed in the medical chart prior to surgery. In the event of an emergent surgery where no recommendations are available, a hematologist should be consulted. In cases of an emergency, it is recommended to infuse either fresh frozen plasma (FFP) or cryoprecipitate to stabilize the patient and transfer to a tertiary center that can manage these patients. FFP can be used in cases of factor IX or XI deficiency. Cryoprecipitate is enriched in vWF, factor VIII, and fibrinogen and can be used in cases of hemophilia A or von Willebrand disease.
Generally, in patients with hemophilia A, B, or von Willebrand disease, specific factor levels should be maintained as high and for as long as clinically indicated based on published guidelines and clinical response to surgery. The prescribed factor is usually infused as a bolus in the morning prior to surgery, with specific factor levels measured before anesthesia induction to confirm that the factor has been administered and the appropriate factor level achieved. Failure to achieve an adequate factor level may be a sign of an inhibitor or inadequate dosing which may require that the surgery be postponed. If the patient has developed an inhibitor the patient may need to be transferred to a center with significant experience in managing inhibitor patients.
Postoperatively, the duration of maintenance therapy depends on the type of surgery performed, ranging from a few days for fairly minor surgical procedures (dental work, simple biopsies) to 2 weeks for more invasive surgery such as abdominal or orthopedic surgery. Factor levels are monitored daily for the first few days and can usually be lowered once surgical hemostasis is achieved (usually by the fourth or fifth day). Once the patient is safe to discharge from a surgical standpoint, it is important to ensure that these patients have an adequate care plan in place for home factor infusion (central line placement, factor delivered to home, self-infusion vs home health nurse infusion) as they will likely require additional days of factor infusion. If a care plan is not in place or not feasible, the patient should remain in the hospital until completion of factor maintenance therapy. Inadequate factor replacement therapy is one of the main risk factor for surgical readmissions due to postoperative bleeding and wound dehiscence in these patients.
Similar principles apply for patients with rare factor deficiencies (fibrinogen, factor II, factor V, factor VII, factor X, factor XI, and factor XIII). Table 54-3 lists the type of factor deficiencies and their treatment options.
TABLE 54-3Treatment Options for Coagulation Factor Deficiencies ||Download (.pdf) TABLE 54-3 Treatment Options for Coagulation Factor Deficiencies
|Deficiency ||Treatment Options |
|Fibrinogen ||Fibrinogen concentrate, cryoprecipitate, FFP |
|Factor II ||PCC, FFP |
|Factor V ||FFP, platelets (contains factor V) |
|Factor VII ||rFVIIa, PCC containing factor VII, FFP |
|Factor X ||PCC, FFP |
|Factor XI ||FFP, factor XI concentrate* |
|Factor XIII ||Factor XIII concentrate, FFP, cryoprecipitate |
The wound healing process is dependent upon a provisional matrix composed of fibrin. Hemostatic defects that limit the formation of a fibrin matrix may lead to wound healing defects resulting in delayed bleeding or reduced rate of wound closure. Patients with hemophilia or other congenital bleeding disorders display delayed bleeding after trauma or surgery if the initial clot that forms is not stable and resistant to breakdown. Furthermore, wound healing is a dynamic process. The initial clot is subsequently remodeled and the ability to reform fibrin must be maintained until the initial fibrin matrix is replaced by the synthesis of extracellular matrix.
Antifibrinolytics such as aminocaproic acid and tranexamic acid are often prescribed as adjunct therapy postsurgery in patients with congenital hemostatic disorders. These agents inhibit tissue fibrinolysis, leading to clot stabilization. The prophylactic use of antifibrinolytics has been shown to reduce postoperative bleeding in cardiac, orthopedic and liver transplant surgery. In patients with hematuria of upper urinary tract origin, antifibrinolytics are not recommended as it can cause intrarenal or ureteral obstruction through clot formation. Of note, there have been case reports of thrombotic complications associated with the use of antifibrinolytics in patients that have chronic DIC syndrome and cancer. Judicious use of these agents is recommended in patients who are known to be prothrombotic (eg, recent thrombotic events, known coronary artery disease, or cancer patients).
The lupus anticoagulant represents a common preoperative issue that generates significant confusion and often leads to delays in surgery. These patients will have an abnormal aPTT and no history of bleeding, assuming there is no other defect reported. The lupus anticoagulant is a misnomer because patients that have this laboratory abnormality do not bleed and are in fact at an increased risk of thrombosis. Lupus anticoagulants are likely to be detected in routine pre-op screening of patients that do not have any bleeding history. Laboratory testing will often document a prolongation of the aPTT. A mixing study of the patient’s plasma with normal plasma will not correct the defect after incubating the plasma for 60 minutes. The only caveat that warrants further consideration is the lupus anticoagulant patient that has a bleeding history or a very prolonged PT. These patients may have a coexisting factor inhibitor or very low prothrombin levels due to the presence of antiprothrombin antibodies that promote the clearance of prothrombin. Consultation with a hematologist will be needed to further define the lab abnormality and provide medical clearance for surgery.
Factors that Increase Risk of Hematologic Complications
There are several patient-specific and procedure-specific risk factors that are known to increase hematologic complications with surgery (Table 54-4).
TABLE 54-4Established Risk Factors for Perioperative Hematologic Complications ||Download (.pdf) TABLE 54-4 Established Risk Factors for Perioperative Hematologic Complications
Type of surgery
Choice of anesthesia
PATIENT-SPECIFIC RISK FACTORS
Hematologic complications are greatly influenced by advanced age. The incidence of venous thromboembolism increases sharply with age. In individuals in the 25 to 30 years age group, the incidence is approximately 1 per 10,000 person-years. In contrast, the incidence increases about 80-fold with nearly 8 per 1000 person-year in the 85 years and older age group. Advanced age is also a risk factor for bleeding. The IMPROVE bleeding risk model which provides an estimate of in-hospital bleeding from the time of admission up to 14 days following admission for an acute medical illness demonstrated that the probability of major in-hospital bleeding for men was 0.1% in the <40 years, 0.2% in the 40 to 84 years, and 0.5% in the ≥85 years. The probability of a clinically important in-hospital bleeding was 0.5%, 1.1%, and 2.2%, respectively.
The prevalence of anemia, a known risk factor for postoperative mortality, also increases with advancing age, especially after the fifth decade of life and exceeds 20% in those 85 years and older. Anemia in the elderly may be due to decreased red cell production from age-related decline in normal bone marrow function, nutritional deficiencies (iron, B12 or folate) from poor dietary intake or decreased erythropoietin production from chronic kidney disease. Inflammatory response related to chronic disease conditions can also causes anemia of chronic inflammation, a disorder mediated by an increase in hepcidin production. Preoperative anemia can result in increased morbidity and mortality, particularly in elderly patients, as the surgery itself stresses the cardiovascular system, resulting in tissue hypoxia from reduced cardiac output and underlying atherosclerosis. This risk can be minimized through the correction of anemia using iron to correct the anemia or through exogenous erythropoietin injection. However, many elderly patients may have a primary marrow defect and not be responsive to such therapy. Underlying MDS or other changes that influence marrow response may affect the elderly and the threshold for providing transfusion support is dependent on the magnitude and extend of other organ dysfunction such as pulmonary, cardiac, vascular, or neurologic problems.
The presence of other comorbidities such as liver and kidney disease also increases the risk of perioperative hematologic complications.
Patients with liver disease are often coagulopathic from decreased hepatic synthesis of procoagulant and anticoagulant clotting factors, impaired hepatic clearance of fibrinolytics, malabsorption of vitamin K from impaired bile salt recirculation, dysfibrinogenemia, thrombocytopenia from hypersplenism and impaired thrombopoietin production, and platelet dysfunction. As both procoagulant and anticoagulant activities are affected, these patients are not “autoanticoagulated.” Instead, these patients remain in a balanced hemostatic state, albeit a more tenuous state, which is easily disturbed by any external stressors, such as surgery. As a result, patients with liver disease are at increased perioperative risk of bleeding and thrombosis.
For patients with mild liver disease (prolongation of INR <2.0) undergoing low- or moderate risk surgery, prophylactic intervention is usually not required. For high-risk surgery or severe liver disease, the correction of factors that are severely depressed may aide hemostasis. However, aggressive therapy with FFP to correct the INR is not feasible and will lead to volume overload in these patients. Recent studies using thromboelastograms to guide therapy have demonstrated that correction of the INR can be replaced by an approach that attempts to correct low fibrinogen, low platelet count and low coagulation factor levels. These patients are often undernourished or exposed to antibiotics. As these patients may be vitamin K deficient, vitamin K replacement therapy can be given to see if this helps to correct the coagulopathy.
Chronic kidney disease is associated with increased perioperative morbidity from impaired hemostasis secondary to acquired platelet dysfunction, leading to uremic bleeding. Both DDAVP and conjugated estrogen have been used, either alone or concurrently, as prophylaxis prior to surgery or for treatment of acute bleeding. As DDAVP has a limited clinical effect due to tachyphylaxis, it is more commonly used prior to minor surgical procedures (eg, biopsies and endoscopies) whereas conjugated estrogen, which has a longer duration of action of up to 10 days, can be used for elective surgery. Depending on the severity of the platelet dysfunction, platelet transfusion may be indicated. Patients with chronic kidney disease are also frequently anemic from reduced erythropoietin production. Besides tissue hypoxia, anemia can also cause platelet dysfunction by several possible mechanisms. Thus, a decrease in hematocrit may further enhance risk for bleeding and should be corrected prior to surgery. Correction of anemia by use of erythropoietin or transfusion may improve platelet function and is an additional strategy to aide hemostasis in uremic patients.
Given the rising incidence of cardiovascular disease, majority of the population are on aspirin and other antiplatelet agents, including GPIIb/IIIa antagonists, which cause defects in platelet aggregation. The concomitant use of antiplatelet and anticoagulant agents increase the risk of bleeding perioperatively. Prior to surgery, these drugs should be discontinued or avoided in the perioperative period, if safe to do so from a cardiovascular perspective. If needed, platelet transfusion may be indicated prior to surgery or in the case of excessive bleeding.
PROCEDURE-SPECIFIC RISK FACTORS
The postoperative risk of bleeding, which is the highest contributor to morbidity and mortality in patients with malignant or nonmalignant hematologic disease, is greatly influenced by the type of surgery. A bleeding risk stratification based on the type of surgical or invasive procedures helps predict postoperative risk of bleeding and guide preoperative management (Table 54-5).
TABLE 54-5Risk for Bleeding with Surgical or Invasive Procedures ||Download (.pdf) TABLE 54-5 Risk for Bleeding with Surgical or Invasive Procedures
|Risk ||Type of Procedure ||Examples |
|Low ||Nonvital organs involved, exposed surgical site, limited dissection ||Lymph node biopsy, dental extraction, cataract extraction, most cutaneous surgery, laparoscopic procedures, coronary angiography |
|Moderate ||Vital organs involved, deep, or extensive dissection ||Laparotomy, thoracotomy, mastectomy, major orthopedic surgery, pacemaker insertion |
|High ||Bleeding likely to compromise surgical result, bleeding complications frequent ||Neurosurgery, ophthalmic surgery, cardiopulmonary bypass, prostatectomy or bladder surgery, major vascular surgery, renal biopsy, bowel polypectomy |
The choice of anesthesia can influence perioperative morbidity and mortality. General anesthesia may reduce myocardial contractibility and cardiac output. This further decreases tissue oxygen-delivery in elderly patients with borderline anemia, and may potentially lead to acute cardiac decompensation, resulting in myocardial ischemia, infarction and/or stroke. Certain inhalational general anesthetic agents can also inhibit the enzymatic activity of glucose-6-phosphate dehydrogenase (G6PD) activity, which leads to acute hemolysis in patients with G6PD deficiency. An awareness of this diagnosis should be communicated to the surgical and anesthetic team and placed in the chart to avoid the use of drugs known to precipitate hemolysis.
As the risk of perioperative complications can vary considerably depending on the underlying hematologic disorder, it is important to identify the disorder and its severity. A careful assessment of the benefits of surgery against the risk of perioperative complications is essential. With appropriate perioperative evaluation and management strategies, these patients should be able to undergo the majority of surgeries with risk reduced by managing known risk factors.
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