PE suspected
Spiral CT (preferred)
Ventilation/perfusion scan
Search for other cause of symptoms
Initiate anticoagulation
Test positive Test indeterminate Test negative
Positive Negative
-or-
Venous ultrasound (consider serial examination)
CT, computed tomography.
Haematopoeitic Disorders rHypercoagulable States 5 1 5
TABLE 65.3 Weight-Based Unfractionated Heparin Dosing Initial Dose
Bolus 60–80 U/kg Infusion 14–18 U/kg/hr Adjustment: aPTTa
<40 2.000 units IV bolus and increase infusion rate by 2 U/kg/hr
40–44 Increase infusion rate by 1 U/kg/hr
45–70 No change
71–80 Decrease infusion by 1 U/kg/hr
81–90 Hold infusion for 30 min, decrease infusion rate by 2 U/kg/hr
>90 Hold infusion for 1 hr, decrease infusion rate by 3 U/kg/hr
IV, intravenous.
aaPTT should be drawn 6 hr after any adjustment to dose.
TABLE 65.4 Alternative Anticoagulants
Mechanism Prophylaxis Therapeutic
Drug of action Use dosing dosing
Enoxaparin Inactivation of factor Xa
Prophylaxis and treatment of DVT/PE
40 mg SC q24h
1 mg/kg SC q12h or 1.5 mg/kg SC
q24h Dalteparin Inactivation
of factor Xa
Prophylaxis and treatment of DVT/PE
5000 units SC q24h
100 U/kg SC q12h or 200 U/kg SC
q24h Fondaparinux Inactivation
of factor Xa
Prophylaxis and treatment of DVT/PE, HIT
2.5 mg SC q24h
7.5 mg SC q24h or 10 mg SC
q24h if
>100 kg Lepirudin Direct
thrombin inhibitor
HIT 0.1 mg/kg/
hr IV
0.4 mg/kg IV bolus, then 0.15 mg/kg/hr IV Argatroban Direct
thrombin inhibitor
Treatment of thrombosis in HIT
2μg/kg/
min IV
DVT, deep venous thrombosis; PE, pulmonary embolism; SC, subcutaneously; HIT, heparin- induced thrombocytopenia; IV, intravenous.
LWBK976-65 LWW-Kollef-educational September 22, 2011 14:42
5 1 6 H A E M A T O P O E I T I C D I S O R D E R S
Clues from the physical examination can yield evidence as to the source of the thrombosis. Multiple sites of ischemia are typical of an embolic phenomenon (but can also be seen in the setting of vasculitis), whereas isolated ischemia is more typical ofin situthrombosis. Further evaluation of suspected arterial thrombosis can be performed with compression ultrasound, although computed tomography angiography is often more helpful.
Treatment of suspected arterial thrombosis should be instituted immediately, as delay in treatment can result irreversible damage due to ischemic tissue. Anticoagula- tion should be initiated as outlined in Tables 65.3 and 65.4, and surgical consultation should be sought for possible operative management.
H Y P E R C O A G U L A B I L I T Y E V A L U A T I O N
Patients in the ICU have many transient risk factors for the development of throm- boembolic disease. Because of this, most instances of thromboembolism do not war- rant workup for an underlying hypercoagulable state. The optimal time for laboratory evaluation of hypercoagulable states is unclear, but is often undertaken approximately 6 weeks to 6 months after the event. Laboratory evaluation in the immediate days to weeks following a thrombosis can yield false results because of the increase in acute- phase reactants associated with acute clot formation, which can result in false-positive tests for hypercoagulable states. However, in the setting of recurrent thrombosis, cere- bral vein or visceral vein thrombosis, and nonembolic arterial thrombosis, further evaluation is warranted. Minimal workup should include evaluation for lupus anti- coagulant, anticardiolipin antibody, and fasting plasma homocysteine level. In cases marked by recurrent thrombosis or cerebral or visceral vein thrombosis, further workup should include a prothrombin G20210A mutation analysis as well as a factor V Leiden mutation analysis. Hematology consultation should be obtained for further evaluation and long-term treatment planning.
C O N D I T I O N S A S S O C I A T E D W I T H D E C R E A S E D P L A T E L E T S A N D H Y P E R C O A G U L A B I L I T Y
There are occasional conditions that present with thrombocytopenia as well as hyper- coagulability. Heparin-induced thrombocytopenia is a serious condition manifested by the formation of antibodies to platelets in response to heparin administration. This condition can cause thrombosis in the setting of severe thrombocytopenia, and is discussed in detail in Chapter 62.
Thrombotic thrombocytopenia purpura is another condition associated with hypercoagulability and thrombocytopenia. This serious condition is the result of a deficiency of or inhibitor to the von Willebrand factor cleaving protease, ADAMTS 13. It is manifested by thrombocytopenia, microangiopathic changes on peripheral blood smear (schistocytes), fever, mental status changes, and varying degrees of renal insufficiency. Treatment is emergent and requires immediate hematology consultation and plasma exchange. This condition is discussed further in the Chapter 61.
Disseminated intravascular coagulation can also present with thrombocytope- nia and coagulopathy in the setting of hypercoagulability. Underlying conditions such as sepsis, ischemia, acidosis, and multiorgan failure can induce a consump- tive coagulopathy, resulting in the formation of diffuse thrombi as well as diffuse hemorrhage.
Haematopoeitic Disorders rHypercoagulable States 5 1 7
S U G G E S T E D R E A D I N G S
Cook D, Douketis J, Crowther MA, et al. The diagnosis of deep venous thrombosis and pul- monary embolism in medical-surgical intensive care unit patients.J Crit Care.2005;
25:314–319.
Review of current data investigating diagnostic modalities for DVT and PE with focus on patients in the critical care setting.
Geerts WH. Prevention of venous thromboembolism in high-risk patients. In:American Society of Hematology Education Program Book.Washington, D.C.: American Society of Hematology;
2006:462–466.
Review of prophylactic modalities for DVT in patients in various clinical circumstances.
Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome.N Engl J Med.2002;10:
752–763.
A review of the pathogenesis, diagnosis, and treatment strategies of the Antiphospholipid Antibody Syndrome.
Nachman RL, Silverstein R. Hypercoagulable states.Ann Intern Med.1993;8:819–827.
A review of the major pathophysiologic mechanisms underlying inherited and secondary hyper- coagulable states and review of the frequency, natural history, diagnosis, and management of the disorders.
Peles S, Pillot, G. Thrombotic disease. In: Pillot G, Chantler M, Magiera H, et al, eds.Hematology and Oncology Subspecialty Consult.Baltimore: Lippincott, Williams & Wilkins, 2004:25–
32.
Edited book chapter describing hypercoagulable disease states, with focus on diagnosis and treat- ment strategies.
Rosenberg RD, Aird W. Vascular-Bed specific hemostasis and hypercoagulable states.N Engl J Med.1999;20:1555–1564.
A review of the pathophysiologic mechanisms underlying coagulation disorders on a cellular level, describing the interaction of coagulation factors with vascular-bed–specific cellular signaling pathways.
Tabatabai, A. Disorders of hemostasis. In: Ahya SN, Flood K, Parajothi S, eds.Washington Manual of Medical Therapeutics.30th ed. Baltimore: Lippincott, Williams & Wilkins, 2001:394–
412.
Edited book chapter describing differential diagnosis, diagnostic strategies, and treatment modal- ities for hypercoagulable states, as well as bleeding disorders.
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