Page 387 - Essential Haematology

Chapter 27 Thrombosis and antithrombotic therapy / 373

thrombosis but the exact mechanisms, types of It is now the treatment of choice for preventing
cancer improved and optimum treatment regimens or treating DVT and the preferred treatment for PE
remain to be elucidated. and unstable angina. Although routine monitoring
is not required, measurement of anti - Xa peak levels
4 hours after injection allows dose adjustment in
selected patients (e.g. in pregnancy, renal failure,
Administration and l aboratory c ontrol gross obesity and in children). Typical treatment
regimens are 200 anti - Xa units/kg once daily or 100
Standard h eparin
anti - Xa units/kg twice daily). LMWH is used for
Continuous intravenous infusion Th is provides the prevention of DVT in both medical and surgical
the smoothest control of heparin therapy and is the patients. It is also the preferred anticoagulant in
treatment of choice where rapid reversal of antico- pregnancy because it does not cross the placenta.
agulation by protamine sulphate may be required Typical once - daily subcutaneous dosage in prophy-
(e.g. in surgical patients or late pregnancy). It is still laxis is 2000 – 2500 units (moderate risk patients),
used for treatment of acute PE but has largely been 4000 – 5000 units (high risk patients) and therapeu-
replaced for this indication and DVT by LMWH. tic doses (mechanical heart valves).
In an adult, dosage of 30 000 – 40 000 units over 24 It is now mandatory for hospitals in England to
hours (1000 – 2000 units/hour with a loading dose have a policy for prevention of DVT and PE for all
of 5000 units) is usually satisfactory. hospitalized patients. LMWHs are the gold stand-

Therapy is monitored by maintaining the APTT ard pharmaceutical agents but oral anticoagulants
usually at 1.5 – 2.5 times the upper limit of the (e.g. dabigatran and rivaroxaban) may supersede
normal value but laboratories need to establish local them.
therapeutic ratios which can be from 1.6 – 2.7 to
3.7 – 6.2. It is usual to start warfarin therapy within
2 days of starting heparin therapy and to discon- Bleeding d uring h eparin t herapy
tinue heparin when the INR has been above 2.0 on Bleeding may be because of excessive prolonged
two successive days. For acute coronary syndromes, anticoagulation or due to an antiplatelet functional
both unfractionated heparin and LMWH are of effect of heparin. Intravenous heparin has a half - life

benefi t when used with aspirin in the prevention of of less than 1 hour and it is usually only necessary
mural thrombosis, systemic embolization and to stop the infusion. Protamine is able to inactivate
venous thrombosis. heparin immediately and for severe bleeding a dose
of 1 mg/100 units heparin provides eff ective neu-
tralization. However, protamine itself may act as an
anticoagulant when in excess.
Low m olecular w eight h eparin
LMWH (there are many commercial preparations)
is given by subcutaneous injection and, as it has a Heparin - i nduced t hombocytopenia

longer half - life than standard heparin, it can be A mild lowering of the platelet count may occur in

given once a day in prophylaxis, or once or twice a the first 24 hours as a result of platelet clumping.
day in treatment (Table 27.5 ). Compared with This is of no clinical consequence (heparin - induced

unfractionated heparin, LMWH has a more pre- thombocytopenia (HIT) type 1). Th e important
dictable dose – response which avoids the need for HIT, type 2, may occur in up to 5% of patients
routine monitoring. Many patients with uncompli- who are treated with unfractionated heparin and
cated DVTs may now be managed at home with paradoxically presents with thrombosis. It results
regular LMWH injections once or twice daily from the binding of heparin to platelet factor 4
according to the preparation. There is a 50% reduc- (PF4) followed by the generation of an immu-

tion in the risk of heparin - induced thrombocyto- noglobulin G (IgG) antibody to the heparin – PF4
penia or osteoporosis. complex, which leads to platelet activation, throm-