Complications
The frequency, size, and symptoms of PE are variable. In patients with known deep vein thrombosis (DVT), silent PE is detected in about 30% to 40% of patients.[179][180]
PE is treated in the same fashion as DVT, unless there are signs of haemodynamic instability (e.g., cardiac arrest, obstructive shock, persistent hypotension); these patients should be treated with primary reperfusion. Selected patients with PE are candidates for inferior vena cava filter.
The risk of bleeding varies according to type of anticoagulant and patient risk factors. In general, bleeding is less with direct oral anticoagulants (e.g., apixaban, edoxaban, dabigatran) when compared with warfarin for the management of venous thromboembolism. Factors associated with bleeding during anticoagulant therapy include older age (>65 years and particularly >75 years), previous bleeding, cancer, metastatic cancer, kidney failure, liver failure, thrombocytopenia, previous stroke, diabetes, anaemia, antiplatelet therapy, poor anticoagulant control, reduced functional capacity, recent surgery, frequent falls, alcohol abuse, and non-steroidal anti-inflammatory drugs.[159] Unrecognised pathological lesions, such as duodenal ulcer, angiodysplasia in the colon, microvascular disease (e.g., a striatal intracerebral bleed in a patient with hypertension), or (rarely) amyloid angiopathy in the central nervous system, contribute to increased risk of major bleeding.[183]
The definition of major and minor bleeding is not standard across studies, and the reported incidence of anticoagulant-related bleeding in the literature varies.
In cases of major bleeding, idarucizumab is approved for reversal of anticoagulant effects of dabigatran; it binds specifically to dabigatran preventing it from inactivating thrombin. Recombinant coagulation factor Xa (andexanet alfa) has been approved in the UK for patients with major or life-threatening bleeding on rivaroxaban and apixaban, although it is only approved for gastrointestinal bleeding in England. Of note, andexanet alfa is not approved for the reversal of edoxaban in the UK and Europe, likely due to low study enrolment of these patients.[184] However, it is approved in Japan.
For patients receiving warfarin, treatment with four-factor prothrombin complex concentrate (if available) in addition to intravenous vitamin K is recommended.[185]
Antibodies may develop to heparin-platelet factor IV complexes starting 5 to 7 days after initial exposure to heparin or as early as <1 day in patients with recent (<30 days prior) heparin exposure.[177] The antibodies aggregate platelets, lead to thrombocytopenia, and might result in acute arterial and venous thrombosis as well as bleeding.
If there is a history of recent heparin exposure, development of HIT can be immediate. It develops in between 1% to 2% of patients treated with therapeutic doses of heparin; however, it is rare when heparin is given subcutaneously to patients as a form of prophylaxis, but is possible and should be evaluated in patients receiving prophylactic heparin with an elevated Warkentin Probability Scale ('4T score'). [ Pretest Probability of Heparin Induced Thrombocytopenia (4-T's score) Opens in new window ]
The incidence of HIT is lower in patients treated with low molecular weight heparin (LMWH). Although there have been several reported cases of fondaparinux-associated HIT, it is a rare occurrence.
Due to the risk of HIT, platelet count should be measured at baseline, then on days 3 and 5, to observe for the development of HIT.
Suspected or confirmed HIT should be managed by promptly discontinuing heparin or LMWH, and substituting a direct thrombin inhibitor such as argatroban or danaparoid.[36] Bivalirudin, desirudin, and fondaparinux have also been suggested as suitable options, but are not licensed for active HIT in the UK.[36]
IHI: anticoagulant toolkit – reducing adverse drug events
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Anticoagulation may be transitioned to warfarin, if a parenteral anticoagulant is initially chosen, when the platelet count returns to baseline.
The Warkentin Probability Scale ('4T score') for HIT can be used to estimate the pretest probability of HIT.[178]
Patients might require very large doses of intravenous heparin and never achieve a therapeutic activated partial thromboplastin time (aPTT).[186] This might be caused by very high levels of clotting factors, such as fibrinogen.
In patients who require extremely large daily doses of unfractionated heparin (i.e., >2500 units/hour) without achieving a therapeutic aPTT, it is recommended that the calibrated anti-Xa activity be measured and used to guide heparin dosing.
In certain patients, such as those with antiphospholipid syndrome, the aPTT value may create a result in the target range with only very low doses of heparin (or even no heparin). Calibrated anti-Xa activity should be used to manage heparin in such cases if heparin is the drug chosen.
Caused by chronic obstruction of venous outflow and/or destruction of venous valves, resulting in venous hypertension from venous insufficiency and/or venous outflow obstruction.[181]
Up to half of patients develop some signs or symptoms of post-thrombotic syndrome and this usually occurs within 2 years of the acute DVT episode.[182]
While the risk of osteoporotic fracture is as high as 2% if unfractionated heparin is given throughout pregnancy, there are only a handful of cases published where osteoporotic fracture occurred in those on low molecular weight heparin.[187]
There is conflicting evidence as to whether this develops in patients during chronic warfarin therapy.[188]
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