Hemostasis and thrombosis involve three separate but intertwined biologic processes:

1. 
   

   Slowed blood flow: Platelets are responsible for the initial adhesion to damaged tissues, and formation of the platelet plug initiates clot formation. This is particularly true for mucosal and cutaneous surfaces. Activated platelets can occur in vascular anomalies and can be predisposed to the initiation of thrombosis, especially around procedures and during inflammation.

   
   
2. 
   

   Endothelial damage: Subendothelial tissue factor or foreign materials (for example, catheters) can initiate the coagulation cascade, an amplifying proteolytic series of events leading to activated circulating coagulation factors. This process culminates in fibrinogen cleavage by thrombin into fibrin, which is crosslinked and forms the fibrin clot. The conversion of soluble fibrinogen to a solid fibrin clot stops further bleeding and allows healing of the underlying injury.

   
   
3. 
   

   Hypercoagulability: The balance of fibrin clot breakdown is controlled by plasmin, which proteolytically cleaves crosslinked fibrin, releasing D-dimers into the circulation and recanalizing the vessel. Fibrinolysis is understudied in vascular anomalies, but hypofibrinolytic states promote thrombosis, whereas hyperfibrinolytic states promote recurrent bleeding and poor wound healing. Hyperfibrinolysis is targeted by antifibrinolytic drugs, such as epsilon-aminocaproic acid or tranexamic acid; these agents are most effective for mucosal bleeding.

Each of these has relevance in vascular anomalies. Slowed blood flow is generally considered for periods of immobility, cardiac insufficiency, and vascular compression. In addition, for patients with vascular malformations, dilation (ectasia) of venous channels and saccular vascular structures creates areas of slowed, swirling, stagnant, or even reversed blood flow. Adequate blood flow is protective from thrombosis by diluting activated clotting factors. By allowing activated platelets and clotting factors to concentrate in areas of slowed blood flow, localized intravascular coagulopathy occurs in slow-flow vascular malformations. Studies comparing intralesional with systemic blood have demonstrated the concentration of coagulopathy within intralesional blood.

Endothelial damage generally refers to surgery, catheter placement, and trauma. Vascular anomalies are lined with abnormal endothelium, allowing exposure of subendothelial collagen and tissue factor and resultant activation of platelets and clotting factors. In healthy circulation, vascular endothelium is coated with antithrombotic proteins, including thrombomodulin and endothelial protein C receptor. The loss of these proteins and their endogenous anticoagulant properties also contributes to thrombotic risk. Furthermore, the main therapies for slow-flow vascular malformations are surgical resection and endovascular sclerotherapy, which trigger additional endothelial injury.

Hypercoagulability refers to the inherent properties of the blood favoring thrombosis. Common inherited causes are factor V Leiden and prothrombin gene mutation G20210A, which occur in 5% and 2% of whites, respectively. Deficiencies in anticoagulant proteins such as antithrombin, protein C, or protein S can be inherited or acquired in the setting of thrombosis. Inflammatory and rheumatologic disorders, especially those associated with antiphospholipid antibodies, are also prothrombotic. Specific laboratory assessment for hypercoagulability is not indicated for all patients with vascular anomalies but should be considered for patients with a family history of thrombosis or a personal history of thrombosis outside of the vascular malformation or severe extensive or recurrent thrombosis.

There are two general types of coagulopathy in vascular anomalies:

1. 
   

   Platelet trapping within vascular tumors

   
   
2. 
   

   Intralesional thrombosis, leading to consumptive coagulopathy in vascular malformations

These are distinct processes occurring in different types of vascular anomalies.

LABORATORY ASSESSMENT OF COAGULOPATHY

Assessment and monitoring of bleeding can be done with widely available laboratory studies. A complete blood count assesses for anemia and thrombocytopenia. Coagulation times, PT, and aPTT measure the time until the fibrin clot forms. Prolongation of these in vitro clotting times may indicate a predilection for bleeding. In vascular anomalies, consumptive coagulopathy is the most common reason for prolonged PT and aPTT. D-dimer measures crosslinked fibrin cleavage products, and elevation indicates activation of the coagulation cascade and fibrinolysis. Many patients have D-dimer elevation at baseline that worsens during thrombosis or inflammation or after sclerotherapy or surgical procedures. Fibrinogen should be specifically measured rather than estimated from PT/aPTT assessments. Although PT and aPTT measure the effects of multiple proteins involved in clot formation, fibrinogen measurement specifically tests for a deficiency of the final protein needed to make a fibrin clot. Low fibrinogen indicates significant consumption and correlates with bleeding risk. These laboratory tests must be assessed preoperatively and far enough in advance to allow time for correction with anticoagulation, which is generally 2 weeks.

Additional laboratory testing can be considered, ideally in a research setting. Whole-blood assays, such as thromboelastography or rotational thromboelastography, have been considered, as have markers of fibrinolysis. Historically a comparison of intralesional to systemic blood showed a concentration of the coagulopathy within the vascular anomaly.

MANAGEMENT OF PERIOPERATIVE BLEEDING RISK

Although bleeding risk is mainly intraoperative, this risk continues postoperatively and should be vigilantly anticipated. Contributions to bleeding risk include a personal history of bleeding and the degree of coagulopathy and vascularity of the malformation to be incised. Anticipatory control of intraoperative bleeding begins weeks before the procedures. A failure to recognize high-flow vascular diagnoses or consumptive coagulopathy can lead to catastrophic bleeding during procedures.

Preoperative embolization should be considered for a reduction in intralesional circulation in fast-flow vascular anomalies. This is common for arteriovenous malformations but should be discussed for any hypervascular-enhancing lesions. Although not generally needed for involuting infantile hemangioma, other vascular tumors such as Enzinger hemangioma and juvenile nasal angiofibroma are resected with less blood loss after embolization.

Although PT/aPTT prolongation and D-dimer elevation are clues to coagulopathy, bleeding risk correlates with deficiency of fibrinogen. Anticoagulation, which typically occurs with low-molecular-weight heparin (for example, enoxaparin, dalteparin, and tinzaparin), will improve coagulopathy over several days. Dosage is titrated until normalization of fibrinogen levels and ranges from 0.5 to 1 mg/kg/dose every 12 hours in most patients. A standard approach is to initiate anticoagulation 2 weeks before the procedure and recheck laboratory testing for coagulopathy 1 week later. If the initial anticoagulation is insufficient to fully correct coagulation tests, higher doses should be considered, and expert consultation is advised to define and reverse the bleeding disorder before the procedure. In most patients anticoagulation is held before the procedure and resumed after surgical hemostasis is established. In high-risk cases anticoagulation can be continued through the procedure. This may seem counterintuitive, but used in this manner for consumptive coagulopathy, anticoagulation is restoring normal hemostasis rather than promoting bleeding. This approach extends to surgical cases beyond the vascular malformation itself. For example, dental extraction can lead to dramatic bleeding if coagulopathy is not corrected before this procedure.

Intraoperatively, close communication with anesthesia and ongoing laboratory monitoring are essential. Fibrinogen levels should be maintained greater than 100 to 150 mg/dl throughout the case with anticoagulation or cryoprecipitate. Volume maintenance is particularly important to vascular surgical cases, but large-volume transfusion can lead to dilutional coagulopathy. An experienced anesthesia, blood bank, and/or hematology team can manage this with fresh-frozen plasma, along with red cell and platelet transfusions. Monitoring and correction of hypocalcemia from citrate infused with transfusions are also important to hemostasis. Other intraoperative techniques to assist locally with hemostasis are covered elsewhere in other chapters, including tourniquet use, topical thrombin, topical antifibrinolytics, and Aquamantys.

Platelet transfusion for thrombocytopenia is also important to hemostasis. An exception to this is Kasabach-Merritt phenomenon associated with KHE. Advances in medical therapy for KHE have replaced surgical treatments in most patients. Platelet transfusion in KHE with Kasabach-Merritt phenomenon will not correct the thrombocytopenia but will fuel platelet trapping within the lesion, leading to rapid engorgement of the tumor and worsening coagulopathy. Platelet transfusion should be reserved for significant bleeding in this disorder. Postoperatively consumptive coagulopathy often worsens. Close monitoring and continued correction are critical to both bleeding prevention and wound healing. Reinstitution of anticoagulation and use of cryoprecipitate are often sufficient.

MANAGEMENT OF PERIOPERATIVE THROMBOTIC RISK