The editors and publisher would like to thank Dr. Greg Stratmann for contributing to this chapter in the previous edition of this work. It has served as the foundation for the current chapter.
Hemostasis is the formation of blood clot at the site of vessel injury. Physiologic hemostasis involves a complex interplay of four components: vascular endothelium, platelets, coagulation factors, and the fibrinolytic system. This intricate system of checks and balances allows blood to maintain its fluidity within a vessel, promotes clot at the site of vessel injury, dismantles clot, and prevents thrombus formation at other sites. If dysfunction of one component or imbalance between components occurs, abnormal bleeding or pathologic thrombosis may occur. Both congenital and acquired disease states, as well as medications, can disrupt the equilibrium of this complex system and lead to bleeding or thrombosis.
Primary hemostasis refers to initial vascular endothelial injury leading to platelet deposition at the site of injury (or platelet plug). Under normal conditions and blood flow, platelets do not adhere to the endothelial surface or aggregate with each other, but with vascular injury, the endothelial matrix is exposed. This initial trigger leads to platelet adhesion to collagen or von Willebrand factor (vWF) via multiple surface receptors.
Platelet activation then plays a critical role in the aggregation of platelets. Integrins that are normally present on the platelet surface in inactive forms are activated and bind multiple ligands, including vWF, collagen, fibrinogen, fibronectin, and vitronectin. The activated platelets degranulate and release agonists that act on G protein–coupled receptors to further propagate aggregation and formation of the platelet plug. These agonists include adenosine diphosphate (ADP), thromboxane A 2 (TxA 2 ), serotonin, epinephrine, and vasopressin. Along with the activated integrins on platelet surfaces, each of these agonists target and activate phospholipase C (PLC). PLC activation leads to the release of large amounts of calcium, which catalyzes degranulation and induces a change in the platelet shape, making them extremely adhesive.
Following platelet activation, the most abundant receptor on the platelet surface, glycoprotein IIb/IIIa (GPIIb/IIIa), undergoes a conformational change and gains high affinity for fibrinogen, thus promoting platelet aggregation and stablization of the platelet plug. In addition, the cytosolic portion of GPIIb/IIIa binds to the platelet cytoskeleton to mediate platelet spreading and clot retraction. By integrating receptor-ligand interactions with cytosolic events, GPIIb/IIIa is the final common pathway for platelet aggregation.
Clotting Cascade and Propagation of the Clot
Proteases cleave inactive precursor proteins (zymogens) to active enzymes that assemble into complexes that subsequently activate thrombin and propagate clot formation. Traditionally, the clotting cascade has been described as consisting of intrinsic, extrinsic, and common pathways. Although this view is useful for providing a structural framework to understand coagulation and to interpret in vivo coagulation tests (e.g., prothrombin time [PT], partial thromboplastin time [PTT]), the current view is that after formation of the platelet plug, coagulation proceeds via an interplay of mechanisms, which include tissue factor (TF) activation of clotting factors, amplification of clotting factors, and propagation of clot formation by thrombin ( Fig. 22.1 ).
The primary physiologic event thought to initiate clotting is the interaction of TF at the site of vascular injury with activated factor VII (factor VIIa). The TF-VIIa complex then activates factors X and IX. Factor Xa then complexes with and activates factor V (which is released from platelet granules during platelet activation) forming the prothrombinase complex. This complex converts a small amount of prothrombin (factor II) to thrombin. This small amount of thrombin amplifies the cascade by activating additional factors V, VIII, XI, and platelets. Factor IXa and factor VIIIa form a complex (the tenase complex) on the surface of activated platelets. The tenase complex activates additional factor X, leading to increased production of the prothrombinase complex and increased thrombin formation. Once sufficient levels of thrombin are available, fibrin is generated from fibrinogen. Finally, to form a strong blood clot, fibrin activates factor XIII to cross-link the fibrin monomers.
Control and Termination of Coagulation
Three main regulatory molecules control coagulation and facilitate the termination of the coagulation cascade: (1) antithrombin (AT) (formerly antithrombin III), (2) TF pathway inhibitor (TFPI), and (3) activated protein C (aPC). AT inhibits thrombin (factor IIa) and factors Xa, IXa, XIa, and VIIa. When heparin binds to AT, a conformational change occurs and the inactivating process is accelerated by over 100-fold. Endogenous heparin is found on normal endothelial cell surface and prevents spontaneous clot formation, thus limiting the coagulation process to only damaged endothelium. TFPI directly inhibits factor Xa and also complexes with factor Xa to inhibit the TF–factor VIIa complex. Protein C becomes activated when thrombin binds to thrombomodulin on the endothelial cell surface as clot progresses. The thrombin-thrombomodulin complex no longer promotes platelet activation or the formation of fibrin, but instead activates protein C. aPC inactivates factors Va and VIIIa, thus inactivating the prothrombinase and intrinsic tenase complexes. This process is greatly enhanced by the presence of protein S.
Under normal physiologic conditions, plasmin circulates in its inactive plasminogen form. Plasminogen activator inhibitor type 1 (PAI-1) is synthesized by endothelial cells and secreted to prevent the activation of plasminogen. Injured endothelium secretes tissue plasminogen activator (tPA), which cleaves plasminogen to its active form, plasmin. Because tPA also binds fibrin, the generation of plasmin takes place on the fibrin clot surface, localizing the action of plasmin to the area of clot. Fibrin is cleaved by plasmin into soluble products (D-dimer, fibrin degradation products), which also inhibit thrombin activity. Like the formation of clot, clot resolution is a highly regulated process. Plasmin that is unbound to the fibrin clot and circulating is inhibited by α 2 -antiplasmin. If plasmin activation goes unchecked, systemic fibrinolysis and massive hemorrhage may develop.
Diseases Associated with Bleeding
Certain hereditary or acquired disorders, systemic diseases, and environmental conditions can predispose a patient to excessive bleeding after tissue injury, including surgery. This is the result of a disruption of the hemostatic process and involves a complex interaction between coagulation factors, platelets, fibrinolysis, and vascular integrity. Patients with less than 20% to 30% normal coagulation factor values or platelet counts of less than 50,000 cells/μL are more likely than patients with normal values to have uncontrolled intraoperative bleeding. Bleeding diatheses vary in clinical presentation depending on what component of the hemostatic system is affected.
Diseases involving coagulation factor deficiencies may present in early childhood with subcutaneous, intramuscular, or intra-articular hemorrhage after only minor trauma. Diseases involving decreased or dysfunctional platelets are typically associated with mucosal bleeding, epistaxis, prolonged bleeding after dental procedures, and menorrhagia. A careful history and physical examination, laboratory evaluation, and consultation with a hematologist when appropriate are necessary to evaluate any patient with suspected bleeding disorders.
Inherited Coagulation Factor Deficiencies
Hemophilia A and B
Hemophilia A and hemophilia B are X-linked recessive disorders that are the most common inherited deficiencies of specific coagulation factors. Hemophilia A is a deficiency of factor VIII and occurs in approximately 1 in 5000 live male births. Hemophilia B is a deficiency of factor IX and occurs in approximately 1 in 30,000 live male births. Severe disease, defined by less than 1% of coagulation factor activity, occurs in approximately two thirds of patients with hemophilia A and one half of patients with hemophilia B. Laboratory evaluation shows a prolonged activated PTT (aPTT) that corrects in mixing studies, with a normal platelet count and PT. Plasma von Willebrand factor antigen (vWF:Ag) is normal in hemophilia, distinguishing factor VIII deficiency from von Willebrand disease (vWD). Many patients with hemophilia A (up to 25%) and some with hemophilia B (approximately 3% to 5%) will develop inhibitory antibodies as a response to exogenous factor. In these cases, the aPTT does not correct in mixing studies and alternative treatment is necessary.
Acquired factor deficiencies are caused by autoantibodies, most commonly to factor VIII. Acquired factor inhibitors can develop in patients who have received infusions of factor concentrates, are pregnant (also see Chapter 33 ), or have underlying systemic disease such as lupus erythematosus or rheumatoid arthritis, or as a drug reaction. In contrast to hemophilia, these acquired factor inhibitors typically occur in adulthood. In addition, mixing studies fail to show correction of the aPTT that is characteristic of hemophilia.
Other Factor Deficiencies
Less common inherited factor deficiencies include deficiencies of factors XI, XII, and XIII. Factor XI deficiency, also known as hemophilia C or Rosenthal disease, is an autosomal recessive disorder that can be associated with bleeding and is characterized by a prolonged aPTT. Factor XII deficiency can result in a prolonged aPTT but is associated with clotting rather than bleeding. Factor XIII is involved in stabilizing the fibrin clot. Patients with factor XIII deficiency present with delayed bleeding after hemostasis, impaired wound healing, and, occasionally, pregnancy loss. Laboratory evaluation shows a normal aPTT and PT with low factor XIII levels.
von Willebrand Disease
vWD is the most common inherited bleeding disorder. The estimated prevalence is 1% of the general population; however, the true prevalence is likely more frequent because of the highly polymorphic von Willebrand gene and variable phenotypes of the disorder. vWF is synthesized by megakaryocytes and endothelial cells. Once released from these cells, it circulates as a series of multimers formed from a basic dimer subunit. The most active forms of vWF are high-molecular-weight multimers that have multiple binding sites for both platelet receptors and subendothelial structures. In normal hemostasis, vWF binds to both platelets and the extracellular matrix at the site of endothelial injury, thus contributing to primary hemostasis by facilitating platelet adhesion. vWF also plays a role in the coagulation cascade and fibrin clot formation by acting as a carrier protein for factor VIII, increasing its concentration and prolonging its half-life. vWD is classified into three types according to vWF levels and protein function ( Table 22.1 ).
|1||Not enough vWF||70-80%||AD||vWF:Ag, vWF:RCo, FVIII|
|2||Qualitative defect of vWF||15-20%||AD|
|A||↓ binding of vWF to platelets, ↓ large multimers||Common||vWF:RCo << vWF:Ag (↓ large multimers)|
|B||↑ binding of vWF to platelets, ↓ large multimers||RIPA (much less ristocetin required for aggregation)||FVIII/vWF concentrate (DDAVP contraindicated)|
|M||↓ vWF function despite normal large multimers||Rare||↓ vWF:RCo compared with vWF:Ag|
|N||↓ binding of VWF to FVIII||Rare|
|3||Absent vWF||Very rare||AR||vWF:Ag|
In addition to the inherited forms for vWD, several disease states are associated with acquired vWD. These consist of autoimmune, lymphoproliferative, myeloproliferative, neoplastic, and cardiovascular disorders. The underlying pathophysiology of acquired vWD includes autoantibodies to vWF, increased clearance of vWF from plasma, enhanced proteolysis after shear stress, and decreased synthesis.
Acquired Coagulation Factor Disorders
Vitamin K Deficiency
Vitamin K is an essential fat-soluble vitamin that is required for the carboxylation of factors II, VII, IX, and X and proteins C and S. Without carboxylation, these factors cannot bind to the phospholipid membrane of platelets during secondary hemostasis. Vitamin K is in dietary sources (leafy greens) and is also synthesized by bacteria in the gastrointestinal tract. Patients who are fasting, who have poor dietary intake or are receiving total parenteral nutrition, and those with impaired intestinal absorption (obstructive jaundice, intestinal ileus or obstruction, or total parenteral nutrition) are susceptible to vitamin K deficiency. Newborns, who have not yet developed normal intestinal flora, and patients undergoing oral antibiotic therapy that alters gut flora are also prone to vitamin K deficiency.
Multiple causes for bleeding diatheses occur in patients with severe liver disease. Primary hemostasis may be impaired because of thrombocytopenia secondary to platelet sequestration by the spleen in patients with portal hypertension and decreased production of thrombopoietic factors. In addition, comorbid conditions such as renal failure and infection can lead to dysfunctional platelets. Secondary hemostasis can be compromised because plasma clotting factors, with the exception of factor VIII, are synthesized in the liver. Laboratory values of platelets, PT, and aPTT may overestimate the bleeding risk in these patients, because the liver is also responsible for the synthesis of anticoagulant factors: protein C, protein S, and AT. Often, this deficiency of both procoagulant and anticoagulant factors leads to a tenuous hemostatic balance, which can be altered by any small disturbance.
Treatment of Clotting Factor Deficiencies
Hemophilia A and Hemophilia B
Patients with known hemophilia should have a thorough preoperative evaluation, including bleeding history, and laboratory evaluation for levels of factor and presence of inhibitors. Given the significant variability of individual response to factor replacement, consultation with a hematologist is necessary to manage perioperative care. Factor concentrates are the treatment of choice for patients with hemophilia A (factor VIII concentrate) and hemophilia B (factor IX concentrate). Dose calculations are targeted to achieve at lease 50% of normal factor activity levels for minor surgery and 80% to 100% of normal factor activity levels for major surgery. Treatment with factor concentrates should continue postoperatively until wound healing is complete. Patient response and the type of surgery determine the necessary duration of treatment.
In resource-limited areas, treatment with cryoprecipitate and fresh frozen plasma (FFP) may be necessary, although not optimal. Cryoprecipitate contains large quantities of factor VIII, vWF, fibrinogen, and factor XIII, but it does not contain factor IX and should not be used for replacement therapy in hemophilia B. Sufficient levels of factor VIII or factor IX levels are difficult to achieve with FFP alone because of inadequate levels of factor and the need for a large volume administration. Prothrombin complex concentrates (PCCs) contain factor IX and can be used for bleeding control in hemophilia B when factor IX concentrates are unavailable. However, PCCs induce a higher thrombotic risk than pure factor IX concentrate and extreme caution should be used when administering concomitant antifibrinolytics. Other adjuvant therapies include desmopressin acetate (DDAVP), which increases plasma levels of factor VIII and vWF and can be useful for hemophilia A, and antifibrinolytics (tranexamic acid [TXA], ε-aminocaproic acid [EACA]), which may decrease the bleeding risk.
von Willebrand Disease
DDAVP is the treatment of choice in type 1 vWD. One dose of DDAVP (0.3 μg/kg) will produce a complete or near complete response in the majority of patients. In addition, cryoprecipitate and intermediate-purity factor VIII concentrates, which both contain high levels of vWF, can be used to attenuate surgical bleeding. DDAVP is contraindicated in type 2b vWD because it causes a transient thrombocytopenia. In addition, patients with severe vWD (type 3) do not respond to DDAVP and should be treated with a combination of factor VIII and vWF concentrates. Antifibrinolytics may also be useful adjuvants in the management of perioperative bleeding in this patient population.
Acquired Coagulation Disorders
Vitamin K deficiency can be treated with vitamin K replacement via oral, intravenous, intramuscular, or subcutaneous administration. In cases of serious bleeding, intravenous vitamin K is the recommended therapy, beginning with a dose of 5 mg. In isolated vitamin K deficiency, correction of the PT will occur within 3 to 4 hours of intravenous vitamin K administration.
Treatment of severe bleeding in the setting of liver failure is most often guided by laboratory abnormalities (also see Chapter 28 ). Platelets are administered for thrombocytopenia, FFP for prolonged PT, and cryoprecipitate may be necessary to treat bleeding in the setting of hypofibrinogenemia (also see Chapter 24 ). Because of the complex balance between deficiencies of procoagulant and anticoagulant factors, routine administration of blood products to correct laboratory values in the absence of bleeding or major surgery is not recommended in these patients. Whether blood product replacement in nonbleeding patients with liver failure should be used for minimal risk procedures, such as central line placement, is not well established.
Treatment of patients with acquired factor inhibitors is complex, as these patients may not respond to standard therapy with factor concentrates. “Bypassing agents” treat bleeding by producing thrombin through pathways that do not require factor VIII or factor IX. “Bypassing agents” are the mainstay of therapy for bleeding patients with high levels of inhibitor in whom administration of factor concentrate is ineffective. Currently available “bypassing agents” include recombinant factor VIIa (rFVIIa) and PCCs. Another treatment strategy in the nonurgent clinical setting is “immune tolerance induction” when patients are exposed to prolonged, high concentrations of factor in an effort to eliminate a coagulation inhibitor.
Both decreased platelet numbers (thrombocytopenia) and qualitative platelet disorders can result in severe bleeding. Inherited platelet disorders are rare congenital diseases that typically affect qualitative function of platelets. In addition to inherited disorders, a multitude of acquired disorders can affect platelet number, platelet function, or both. Both inherited and acquired disorders of platelet function are characterized by prolonged bleeding time and abnormal platelet function tests.
Low platelet counts can be the result of decreased platelet production, increased destruction, or sequestration. Decreased platelet production in the bone marrow occurs in myelodysplastic syndromes, infections (especially in the setting of sepsis), and nutrient deficiencies. Patients with these disorders typically present with pancytopenia because production of all cell lines in the bone marrow is impaired. Other causes of impaired production of platelets include immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) and drug-induced bone marrow suppression. Peripheral platelet destruction by antiplatelet antibodies can be induced by certain medications or ingested substances, as well as in the setting of specific autoimmune diseases. Heparin-induced thrombocytopenia (HIT) occurs in less than 5% of patients exposed to heparin. Antibodies to platelet factor 4 can cause thrombocytopenia and platelet activation, potentially leading to life-threatening arterial and venous thrombosis. Increased platelet consumption within thrombi is seen in disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP-HUS). Diseases that cause splenomegaly or splenic congestion through portal hypertension (e.g., cirrhosis) lead to sequestration of platelets in the spleen, inhibiting their release into circulation.
Multiple disorders of pregnancy result in thrombocytopenia including gestational thrombocytopenia, preeclampsia, and pregnancy-associated hypertensive disorders (also see Chapter 33 ). The most severe of these disorders is the HELLP syndrome (hemolysis, elevated liver function test results, low platelet counts), which necessitates emergent delivery before life-threatening maternal complications occur.
Qualitative Platelet Disorders
Even with adequate platelet numbers, poor function can increase bleeding risk and affect measures of platelet aggregation. Several common drugs impair platelet function including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), alcohol, dipyridamole, and clopidogrel. Uremia, when severe, is associated with increased clinical bleeding. Proposed pathophysiologic mechanisms include intrinsic platelet metabolic defects, impaired platelet granule release, and impaired platelet–endothelial cell interactions. Normal platelet function is also impaired in conditions with high levels of abnormal circulating proteins (multiple myeloma, dysproteinemia, transfused dextran solutions). Many rare conditions involve inherited disorders of platelet function. Glanzmann thrombasthenia is an autosomal recessive disorder characterized by defective GPIIb/IIIa receptors on platelets leading to impaired platelet aggregation. Giant platelet disorders include platelet glycoprotein abnormalities, as in Bernard-Soulier syndrome. Wiskott-Aldrich syndrome is an X-liked recessive disorder in which patients have immunodeficiency, severely dysfunctional platelets, and thrombocytopenia. This syndrome is an example of a storage pool disorder, in which granule deficiencies lead to impaired platelet aggregation.
Treatment of Platelet Disorders (Also See Chapter 24 )
In the nonbleeding patient, treatment of thrombocytopenia in the form of platelet transfusion is usually withheld until the platelet count is less than 10,000 cells/μL. In the patient who is actively bleeding or requires surgical intervention, platelet transfusion is recommended to a goal of 50,000 cells/μL, or in some cases, such as intracranial hemorrhage or neurosurgery, 100,000 cells/μL. A major concern with the transfusion of platelets is the potential for human leukocyte antigen (HLA) or human platelet antigen antibodies to form. If multiple platelet transfusions are expected, platelets should be HLA-matched whenever possible. For patients with normal platelet counts but suspected dysfunctional platelets, administration of platelets is often ineffective because the patient’s underlying condition causes transfused platelets to function abnormally. In these cases, DDAVP may be effective.
Diseases Associated with Thrombosis
Development of venous thrombosis (most commonly deep venous thrombosis [DVT] or pulmonary embolus) is a common occurrence in the surgical population and leads to increased morbidity and mortality rates. The classic teaching for the pathogenesis of venous thromboembolism (VTE), often referred to as Virchow triad, proposes that VTE occurs as a result of (1) stasis of blood flow, (2) endothelial injury, and (3) a hypercoagulable state (inherited or acquired).
Patients with inherited thrombophilia (deficiencies of protein C, protein S, and AT; factor V Leiden and prothrombin gene mutations) have an increased tendency for VTE. Numerous other conditions such as malignancy, pregnancy, immobilization, trauma, DIC, antiphosholipid syndrome, infection, drugs (e.g., oral contraceptives), and recent surgery also predispose patients to VTE.
Hereditary Hypercoagulable States
Factor V Leiden and Prothrombin Gene Mutation
The most common inherited thrombophilias are the factor V Leiden mutation and the prothrombin gene mutation, accounting for 50% to 60% of cases. Individuals with factor V Leiden have an abnormal mutation of factor V that is resistant to the action of aPC. aPC regulates the coagulation process by inhibiting factor V from forming excessive fibrin in normal individuals. The prothrombin gene mutation (prothrombin 20210) leads to overproduction of prothrombin (factor II) and makes the blood more likely to clot. Individuals with factor V Leiden or the prothrombin gene mutation are at increased risk of developing DVTs, with homozygotes having the highest risk. Despite the increased relative risk, the absolute risk of blood clots in these patients remains low in the absence of other risk factors for hypercoagulability.
Protein C and Protein S Deficiencies
Under normal physiologic conditions, aPC inactivates factors Va and VIIIa (enhanced by protein S). In addition, aPC acts directly on cells to protect the endothelial barrier function and also has antiinflammatory activities. Protein C deficiency is an autosomal dominant trait affecting approximately 1 in 500 individuals in the general population. Clinical manifestations of the deficiency include VTE, neonatal purpura (in homozygous neonates), fetal loss, and warfarin-induced skin necrosis. Protein S is a cofactor for aPC and is synthesized by hepatocytes, endothelial cells, and megakaryocytes. Forty to 50% of protein S circulates as the free form, the only form with aPC cofactor activity. In the presence of protein S, aPC inactivates factors Va and VIIIa at an accelerated rate. Protein S also serves as a cofactor for protein C enhancement of fibrinolysis and can directly inhibit prothrombin activation. Individuals with protein S deficiency present similarly to those with other inherited thrombophilias and are at increased risk of VTE, superficial thrombophlebitis, and pulmonary embolism (PE).
Both protein C and protein S deficiencies can be acquired secondary to underlying disease. Acquired protein C deficiency can be seen in liver disease, severe infection (especially meningococcemia), septic shock, and DIC. Acquired protein S deficiency has been associated with pregnancy, use of oral contraceptives, DIC, human immunodeficiency virus (HIV) infection, nephrotic syndrome, and liver disease.
Acquired Hypercoagulable States
The antiphospholipid (antibody) syndrome (APS) is a condition characterized by both venous and arterial thromboses or recurrent pregnancy complications (also see Chapter 33 ). Patients with this syndrome have persistent circulating antiphospholipid antibodies (aPLs), which include lupus anticoagulant, anticardiolipin antibody, or anti-β2GPI antibodies. It is one of the few prothrombotic states in which arterial and venous thromboses occur. Most cases of APS are sporadic or acquired. Rarely, the condition runs in families; yet it does not exhibit a clear pattern of inheritance.
DVT is the most common venous thrombosis and stroke is the most common arterial thrombosis. Diagnosis is made by clinical criteria (arterial/venous thromboses, recurrent pregnancy complications) and by the presence of one or more of the three aPLs detected on two or more occasions at least 12 weeks apart. Patients who have persistently positive aPLs (especially those with multiple differing aPLs), who present with arterial thromboses, or who have recurrent thromboses in the setting of anticoagulation are most likely at risk for thrombosis. The lupus anticoagulant, although often found in patients with systemic lupus erythematosus, can also be associated with medications (phenothiazines, phenytoin, hydralazine, quinine, and antibiotics), inflammatory bowel disease (Crohn disease and ulcerative colitis), infections, and certain kinds of tumors. Catastrophic APS (CAPS) is a rare accelerated form of APS in which patients present with coagulopathy, ischemic necrosis of the extremities, and multiorgan failure in the setting of positive circulating aPLs and histopathologic evidence of small vessel occlusion. Although CAPS occurs in less than 1% of patients with APS, mortality rate is approximately 30%. Early recognition and treatment with anticoagulation and immunosuppressant therapy are paramount to survival.
Disseminated Intravascular Coagulation
DIC is an acquired disorder caused by an underlying condition (most commonly, sepsis) that is characterized by widespread systemic activation of coagulation (also see Chapter 24 ). This results in uncontrolled intravascular thrombin generation and fibrin deposition in small blood vessels. The formation of microvascular thrombi ultimately leads to end-organ dysfunction and multiorgan failure. Excessive consumption of circulating coagulation factors, platelets, and fibrinogen occurs simultaneously with microvascular thrombi formation, which can result in life-threatening bleeding. A patient with DIC may present with both thrombotic and hemorrhagic complications.
No single laboratory test identifies DIC; however, a combination of laboratory tests in the setting of a condition known to cause DIC can be sufficient for diagnosis ( Table 22.2 ). The most common laboratory abnormalities associated with DIC are thrombocytopenia, elevated fibrin degradation products (D-dimers), prolonged PT and aPTT, and low fibrinogen. Because laboratory abnormalities in DIC can be seen in other conditions such as massive blood loss, liver failure, HIT, and thrombotic microangiopathy, a scoring system has been developed by the International Society on Thrombosis and Hemostasis (ISTH). The ISTH scoring system uses simple laboratory tests (platelet count, PT, aPTT, fibrinogen, D-dimer) plus the presence of a triggering underlying condition to diagnose DIC. It has a high sensitivity and specificity (91% and 97%, respectively) and is an independent predictor of mortality risk.