CLASSIFICATION:-
It can be classified as
Primary - without any related disease.
Secondary – in conjunction with autoimmune diseases like SLE .
Catastrophic APS (CAPS) – Rapid multi organ failure due to thrombosis leading to death.
AETIOLOGY:-
Normal person may have antibodies. The triggering factors are:-
Infections- People with Syphilis ,HIV infection, Hepatitis C, Malaria.
Medications- Antihypertensive like hydralazine , antiepileptic like phenytoin, antibiotics like amoxicillin. Cocaine, procainamide, quinine may cause.
Genetics – Although APS has been reported to occur in multiple members of the same family, no clear inheritance pattern has been identified and no gene has been found to be the sole cause of this condition. One report in 1999 studied families with more than one affected member, examined possible modes of inheritance, and examined links with certain genes. In seven families 30 out of 101 family members met diagnostic criteria for the syndrome. The data were fitted best by either a dominant or co dominant models.
PATHOGENESIS:-
Antiphospholipid syndrome is an autoimmune disease in which “antiphospholipid antibodies”(Anticardiolipin antibodies and Lupus anticoagulant) react against protein that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases , it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies are associated with thrombosis and vascular disease.
Anti-ApoH and a subset of Anti-cardiolipin antibodies bind to ApoH , which in turns inhibits Protein C, a glycoprotein with regulatory function upon the common pathway of coagulation(by degrading [Va factor]).
LAC antibodies bind to prothrombin, thus increasing its cleavage in thrombin, its active forms.
In APS there are also antibodies binding to Protein S, which is a co-factor of protein C. Thus Anti-Protein S antibodies decrease Protein C efficiency.
Annexin A5, which forms a shield around negativity-charged phospholipids molecules, thus reducing their availability for coagulation. Thus Anti-annexin A5 antibodies increase phospholipids-dependent coagulation steps.
The Lupus anticoagulant antibodies are those that show the closest association with thrombosis, those that target ?2GP1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to higher titres (> 40 GPLU or MPLU). Patients with both Lupus anticoagulation antibodies and moderate/high titer anticardiolipin antibodies show a greater risk of thrombosis than with one alone.
INCIDENCE:-
The aPL antibodies are found in 30% cases of SLE. The aPL antibodies may be found in 1-5% of normal individuals. There is no racial predisposition of Primary type. It is more common in young adults(30-45 yrs). Primary APS accounts for over 50% cases. Some studies indicate that aPL antibodies may play a role in approximately one third of strokes in persons under age of 50.A female predominance causing secondary APS parallels APS with SLE and other connective tissue disease .After age of 60 incidence is rare.
CLINICAL FEATURES:-
APS usually shows up for the first time as vascular thrombosis or embolism or as recurrent pregnancy loss. Thrombocytopenia , certain skin problems, neurological signs, heart valve disease and certain autoimmune diseases have also have been noted in association with APS. Pulmonary hypertension and sensory- neural hearing loss have been noted in some individuals with APS as well.
Conditions associated with APS include:
1. Systemic Vascular Thrombosis
While the deep veins of the legs are most frequent sites of thrombosis, thromboemblism can involve virtually any vein or artery. Deep vein thrombosis tends to be most common finding, occurring in half of affected individuals. Other sites of venous thrombotic events include the veins of the lungs (due to pulmonary embolism, a clot that typically has dislodged from a vein below the pulmonary veins and lodged in a pulmonary veins), thoracic veins(veins in or above the chest that carry blood to the heart including the superior vena cava, or jugular vein), and abdominal or pelvic veins.
A risk of recurrent thrombi is associated with APS as well. Most studies suggest that individuals who have a recurrent episode will have it in a similar blood vessel type. For example, indivisuals who have a stroke initially will most often have a stroke if they have a recurrence. Nonetheless, individuals are reported who have had different types of thrombosis events.
A deep vein thrombosis( DVT) can form in the arm or leg after a long journey, or in some women, after starting the contraceptive pill. Clots in the veins can cause thrombophlebitis of the legs with pain in the thigh or calf, swelling of the leg , and sometimes a visible red, thickening blood vessel. Damage to the valves of lower limbs may impair the upward venous flow leading to chronic venous insufficiency causing chronic swelling and discoloration of leg. Thrombosis can also affect vital organs such as the eye, liver and kidney.
2. Pregnancy Loss and Other Complications
APS is associated with miscarriages as well as other complications of pregnancy. Most studies have estimated the prevalence of aPL antibodies among pregnant women at 5 percent or less, most of these women do not have any signs or symptoms of APS. Around 10-20 percent of women with multiple pregnancy loses are thought to have APS.
Women with APS often have a history of recurrent (usually defined as three or more) pregnancy losses. Pregnancies occurring in women with APS are at increased risk of prematurity , slower than expected growth of the fetus, and preeclampsia. Pregnant women with APS are also more prone to develop deep vein thrombosis during pregnancy or puerperium .
One miscarriage is a disaster. Two is worse. Imagine the suffering of women who have 3,5,7 or even 12 pregnancy losses, and sometimes as late as the late few weeks of their pregnancy.
We now know that Hughes Syndrome is the most common treatable cause of recurrent miscarriage. Future more, late pregnancy loss, fortunately an unusual problem in pregnancy, is very strongly associated with Hughes Syndrome as is pre-eclampsia, placental abruption and intra-uterine growth restriction.
For the sake of a simple blood test, patients with miscarriage or late pregnancy loss can be tested for Hughes Syndrome. Treatment of these patients has proved one of the true success of modern medicine , the successful pregnancy rate rising from a previous low of fewer than 20% to figures now in the region of 75-80% success rate.
3. Thrombocytopenia
An association with immune thrombocytopenia has been established. This occurs to varying degrees in many as 50% of individuals with APS. Because platelets help the blood to clot, thrombocytopenia can sometimes cause a bleeding disorder in an otherwise healthy person as bleeding from gum, nose and skin. However in APS thrombocytopenia is usually moderate and is rarely significantly enough to cause bleeding complications or affect anticoagulant therapy.
4. Skin Disorders
Certain skin conditions have also been observed in APS. These include livedo reticularis (mottled discolouration of the skin), ulcers on the skin, usually on the legs, and sometimes skin necrosis .
Many Hughes Syndrome patients complain of ‘cold circulation’ and this sometimes manifest as a blotchy appearance of the skin of the arms and legs, described in medical textbooks as “livedo reticularis” or “corned beef skin”. It can also cause repeated sores and bumps (nodules) of the skin.
5. Stroke and Other Neurological Disorder
Stroke is associated with APS as are some other neurological conditions. In addition to cerebrovascular thrombosis , embolic stroke can also occur. Multiple strokes can sometimes leads to a condition called multi-infarct dementia.
Other neurological problems have been reported in people with aPL antibodies, although they are not as strongly associated with APS as stroke. These include seizures, chorea , migraines, Guillain-Barre syndrome, diabetic peripheral neurotherapy, transverse myelitis and conditions similar to multiple sclerosis. Evidence for an association with cognitive dysfunction is growing.
There are many cause of strokes- for instance hypertension but most surveys show that 1 in 5 young strokes (under the age of 45) are now associated with Hughes Syndrome(APS). Now, in the age of easy diagnoses of Hughes Syndrome, many patients are not receiving adequate anti-coagulant treatment of their “sticky blood” , and suffering from early mini-strokes or TIAs (transient ischemic attacks) or more permanent strokes.
Some people with Hughes Syndrome develop a syndrome which is very similar to multiple sclerosis where they have numbness or pins and needles, double vision or loss of part of the field of vision, and have difficulty in walking. Consequently one of the main alternative diagnosis in patients with Hughes syndrome is multiple sclerosis.
