Page 2368 - Hematology_ Basic Principles and Practice ( PDFDrive )

2110 Part XII Hemostasis and Thrombosis

Warfarin has numerous drug interactions including many com- considered. Although not formally evaluated in randomized trials,
monly administered medications. Noninteracting medications should this strategy likely reduces the initial risk of bleeding while eliminat-
be prescribed preferentially in patients receiving warfarin to avoid ing the long-term increased risk of DVT associated with permanent
adverse events. When noninteracting medications are unavailable, caval interruption. In contrast, patients who have a persistent major
increased frequency of INR monitoring and dose adjustments risk factor for bleeding may be considered for insertion of a perma-
enhance safety. Warfarin is contraindicated during pregnancy, but nent IVC filter because the mortality rate associated with major
may be used during breastfeeding. bleeding during therapeutic anticoagulation is approximately 20%.
This procedure is associated with a significant risk of immediate
worsening of leg symptoms because of blockage of the IVC by
Direct Oral Anticoagulants thrombus and a long-term increase in the risk of recurrent DVT.
DOACs that target thrombin (dabigatran) and factor Xa (rivaroxa-
ban, apixaban, edoxaban) are available for the treatment of acute Thrombolytic Therapy for Massive
VTE. These agents do not require routine anticoagulation monitor- Pulmonary Embolism
ing and have fewer interactions with food and drugs compared with
warfarin. Large phase III clinical trials have demonstrated that dabi- Thrombolytic therapy with streptokinase, urokinase, or t-Pa is more
gatran, rivaroxaban, apixaban, and edoxaban are noninferior to the effective than UFH alone in correcting the angiographic defects
combination of LMWH/warfarin for the treatment of acute VTE. produced by PE, and may be better than UFH in preventing death
Treatment with LMWH is given for at least 5 days before dabigatran in patients with massive PE associated with shock. Based on these
or edoxaban. DOACs should be avoided in patients with severe renal findings, thrombolytic therapy is the treatment of choice for patients
impairment (creatinine clearance <30 mL/min) and used with with massive PE associated with cardiovascular collapse.
caution in those with weight above 120 kg, body mass index >40 kg/ Bleeding occurs more frequently with thrombolytic therapy than
2
m , or active malignancy because of a lack of clinical efficacy and with UFH. The risk of hemorrhage increases with the duration of
safety data in these populations. thrombolytic infusion and usually occurs at a site of previous surgery
or trauma. Intracranial hemorrhage occurs in approximately 1% of
patients at risk, approximately twice as frequently as with UFH
Duration of Treatment treatment.
The optimal duration of oral anticoagulant therapy for treatment of
VTE is unknown. Patients with VTE provoked by a clear transient Catheter-Directed Thrombolysis for
risk factor are generally treated for 3 months. Patients with unpro- Deep Vein Thrombosis
voked (idiopathic) VTE should be treated for a minimum of 3
months, with consideration of extended therapy especially for patients Catheter-directed thrombolysis (CDT) involves direct injection of a
at low bleeding risk in whom the clinical benefit of preventing VTE thrombolytic agent through a catheter into the vein affected by DVT,
recurrence outweighs the risk of bleeding. Patients with a persistent, which can also be combined with mechanical thrombus removal. In
major risk factor for recurrence (e.g., malignancy, immobility) and a small nonblinded randomized study, CDT reduced the risk of
patients who prefer to decrease their thrombotic risk should receive postthrombotic syndrome but not health-related quality of life after
anticoagulation for longer periods or indefinitely with regular reas- 24 months of follow-up compared with standard therapy. It has not
sessments of the benefits and risks of ongoing therapy. At this time, been shown to reduce the risk of PE or mortality, and increases the
there are no absolute predictors of recurrence, but recurrence appears risk of bleeding. At present there is insufficient high-quality evidence
to be more common in male patients and those with an elevated supporting a net clinical benefit of CDT given the bleeding risk.
D-dimer assay at or around the time of anticoagulant discontinua- CDT may be considered at centers with technical expertise in CDT
tion. The relationship between residual venous obstruction on in consultation with a thrombosis expert for select patients presenting
ultrasound at the completion of initial treatment and recurrence risk with recent (less than 14 days) iliofemoral DVT with severe symp-
requires further study. toms and low bleeding risk.
Decisions regarding extended anticoagulant therapy should
incorporate counselling regarding the expected risks and benefits, and
patient values and preferences. Extended treatment reduces the risk Thromboendarterectomy for Pulmonary Embolism
of recurrent VTE by at least 80% with a small increased risk of
bleeding. When prescribing apixaban, a reduced dose (2.5 mg twice Thromboendarterectomy is effective in selected cases of CTEPH with
daily) is used for secondary VTE prevention after initial 6 months of proximal pulmonary arterial obstruction. Urgent pulmonary embo-
anticoagulant therapy. Low-dose aspirin reduces the risk of recurrence lectomy is usually reserved for patients with a saddle embolism lodged
by approximately 30%. However, it is not considered an equivalent in the main pulmonary artery or for those with massive embolism
alternative to anticoagulant therapy given the reduced efficacy and whose blood pressure cannot be maintained despite thrombolytic
should be reserved for patients wishing to discontinue anticoagulants therapy and vasopressor agents. Although this procedure can be suc-
who have no contraindication to aspirin therapy and/or have another cessfully performed by experienced surgical teams, in inexperienced
indication for aspirin. hands it is associated with high complication and mortality rates.
Patients with repeated episodes of PE and significant chronic pulmo-
nary hypertension with right ventricular compromise should be
Inferior Vena Cava Filter anticoagulated and monitored. If pulmonary pressures do not
decrease, patients should be evaluated for surgical fitness. If deemed
Anticoagulants are effective in reducing mortality from PE. However, necessary, thromboendarterectomy should be carried out in centers
some patients have relative or absolute contraindications to antico- with expertise with optimal perioperative management, within which
agulant therapy. In these cases, there may be a role for inferior vena the likelihood of success of the procedure is high.
cava (IVC) filters (see Chapter 143). IVC filters do not treat VTE
but are used to prevent PE in patients with DVT who cannot receive
adequate anticoagulant therapy. In patients with active bleeding or a VENOUS THROMBOSIS IN PREGNANCY
transient risk factor for bleeding (e.g., surgery), insertion of a tem-
porary IVC filter followed by its removal and subsequent therapeutic The risk of VTE is increased during pregnancy and the postpartum
anticoagulation when the bleeding risk is diminished should be period. DVT is more common than PE and affects the left leg in