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Chapter 27 Thrombosis and antithrombotic therapy / 369

Infl ammation pholipid antibody. The predominant antibodies in
this disorder are directed against protein antigens
This up - regulates procoagulant factors, down -

that bind to anionic phospholipids, such as β 2 -
regulates anticoagulant pathways, particularly
glycoprotein 1 ( β 2 - GPI - 1) and prothrombin.
protein C. Thrombosis is particularly likely in

One antiphospholipid antibody is the ‘ lupus
’
inflammatory bowel disease, Beh ç et s disease, sys-

anticoagulant ’ (LA) which was initially detected in
temic tuberculosis, systemic lupus erythematosus

patients with SLE, and is identified by a prolonged
(SLE) and diabetes.
plasma APTT which does not correct with a 50 : 50
mixture of normal plasma. Paradoxically, in view of
Blood d isorders its name, it is associated with venous and arterial
thrombosis. A second test dependent on limiting
Increased viscosity, thrombocytosis, altered platelet quantities of phospholipid (e.g. the dilute Russell s
’
membrane receptors and responses are possible viper venom test) is also used in diagnosis. Whereas
factors for the high incidence of thrombosis in lupus anticoagulants are reactive in the fl uid phase,
patients with polycythaemia vera and essential other antiphospholipid antibodies, such as anticar-
thrombocythaemia. Testing for the JAK2 V617F diolipin antibodies and antibodies to β 2 - GPI - 1, are
mutation may indicate an otherwise unsuspected identified by solid phase immunoassay. Both solid

myeloproliferative disease in patients with hepatic phase assays and coagulation tests for LA should be

or portal vein thrombosis. There is a high incidence used in the diagnosis of APS.
of venous thrombosis, including thrombi in large As well as patients with SLE, antiphospholipid
veins (e.g. the hepatic vein) in patients with parox- antibodies are also found in other autoimmune dis-
ysmal nocturnal haemoglobinuria. An increased orders particularly of connective tissues, lympho-
tendency to venous thrombosis has been observed proliferative diseases, post - viral infections, with
in patients with sickle cell disease, with post - certain drugs including phenothiazines and as an
splenectomy thrombocytosis and those with a ‘ idiopathic ’ phenomenon in otherwise healthy sub-
paraprotein. jects. Arterial thrombosis may cause peripheral limb
ischaemia, stroke or myocardial infarct. Venous
Oestrogen t herapy thrombosis includes DVT, PE and thrombosis in
vessels supplying the abdominal organs. As with
Oestrogen therapy, particularly high dose therapy, other causes of thrombophilia, recurrent abortion
is associated with increased plasma levels of factors caused by placental infarction is also associated
II, VII, VIII, IX and X and depressed levels of (Table 27.3 ). Thrombocytopenia may be present

antithrombin and tissue plasminogen activator

in the vessel wall. There is a high incidence of post-
operative venous thrombosis in women on high
Table 27.3 Clinical associations of lupus

dose oestrogen therapy and full dose oestrogen -
anticoagulant and anticardiolipin antibodies.

containing oral contraceptives. The risk is much less
with low dose oestrogen contraceptive preparations. Venous thrombosis: deep venous thrombosis/
Hormone replacement therapy also increases the pulmonary embolism, renal, hepatic, retinal veins
risk of thrombosis, largely obviated by the use of
Arterial thrombosis
low oestrogen preparations.
Recurrent fetal loss
The a ntiphospholipid s yndrome Thrombocytopenia
Livedo reticularis

The antiphospholipid syndrome (APS) can be
defined as the occurrence of venous and arterial

NB. Recurrent fetal loss may also occur in other types of
thrombosis and/or recurrent miscarriage in associa-
thrombophilia.
tion with laboratory evidence of persistent antiphos-