Further Outpatient Care
Interval care includes the following:
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History and physical examination for signs and symptoms of thrombotic or vasospastic events
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Laboratory testing for monitoring anticoagulant therapy, antiphospholipid antibody testing, and, in the case of secondary antiphospholipid syndrome, underlying disease activity
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Imaging and Doppler studies for follow-up of previous thrombotic process
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Dietary and lifestyle counseling
Further Inpatient Care
Further inpatient care in patients with antiphospholipid (aPL) antibody syndrome (APS) is only on an as-needed basis for management of thrombotic events but may include the following:
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Imaging studies
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Medical therapy
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Invasive procedures for thrombolytic therapy
Further inpatient care is indicated if a catastrophic antiphospholipid antibody syndrome (CAPS) occurs.
Inpatient & Outpatient Medications
See the list below:
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Antiplatelet therapy, such as administration of aspirin, dipyridamole, hydroxychloroquine, ticlopidine, clopidogrel, or combinations of these agents
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Vasodilator and/or antiplatelet therapy, such as pentoxifylline or cilostazol
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Vasodilators, such as niacin or topical nitroglycerin (nitropaste)
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Anticoagulation therapy, such as warfarin, heparin, or low molecular weight (LMW) heparin [99, 100, 101]
Warfarin sensitivity is conferred by the presence of a cytochrome oxidase P-450 mutation (CYP2C9) and can be associated with severe bleeding (*3 isoleucine to leucine in 10% of Caucasians; *4 asparagine to glutamine in 3% of African Americans).
The presence of an antiphospholipid antibody accentuates the prothrombotic state that exists when warfarin is withdrawn (because of low protein C synthesis and the presence of plasminogen activator inhibitors).
Abrupt withdrawal of warfarin by the physician or by the patient through noncompliance may result in a thrombotic event.
Coverage with LMW heparin during the period of warfarin withdrawal (approximately 3-5 d until protein C levels return to normal) may reduce this risk.
The prothrombin time (PT), standard partial thromboplastin time, or both may be prolonged in the presence of an antiphospholipid antibody, thus diminishing the accuracy of these assays in monitoring of the effectiveness of anticoagulant therapy.
The PT/international normalized ratio (INR) assays are also inaccurate in the presence of the lupus anticoagulant (LAC) and may provide results that vary according to the source of thromboplastin (manufacturer or lot-to-lot).
Chromogenic factor X levels and the prothrombin–proconvertin time more accurately reflect the level of anticoagulation in patients with a LAC who are on warfarin therapy.
The adequacy of therapy with LMW heparin should be assessed with a plasma anti–factor Xa assay, which measures the inactivation of factor Xa. Ideally, the sample should be drawn 3 hours post-injection, kept at 4°C, and processed as soon as possible.
Antiphospholipid antibody can bind to platelet factor 4 (PF4), and/or β2-glycoprotein I [GPI]) in the enzyme-linked immunosorbent assay (ELISA) test for heparin antibodies. A false-positive test in the presence of antiphospholipid antibody–associated thrombocytopenia may be falsely interpreted as heparin-induced thrombocytopenia (HIT), and anticoagulation may be inappropriately halted. Confusion may be avoided by obtaining this test prior to exposure to heparin. [102]
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Immunomodulators, such as intravenous immunoglobulin or rituximab
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Therapy for thrombocytopenia, such as steroids, danazol, dapsone, intravenous immunoglobulin (IVIG), or vincristine
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Therapy for dyslipoproteinemia or hyperlipidemia: This may include statin drugs or niacin. [95]
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Dietary supplementation with folic acid, vitamin B-12, or both for patients with hyperhomocysteinemia: See Medication and the therapeutic algorithm in the image below.
One set of suggested algorithms for the workup and treatment of patients with antiphospholipid antibody syndrome. This should not be considered dogmatic because laboratory evaluation is not standardized and treatment remains empiric and controversial. Laboratory testing is not recommended in healthy asymptomatic individuals with no risk factors and a negative family history.
Transfer
Patients with CNS, cardiovascular, or peripheral vaso-occlusive events may need to be transferred to facilities with appropriate support personnel, experience, and equipment.
Patients with catastrophic antiphospholipid antibody syndrome require admission to an ICU, high-level supportive care, and multiple consultative services.
Deterrence/Prevention
See the list below:
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Adequate medical therapy
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Patient education
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Monitoring for new events
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Monitoring for drug adverse effects and toxicity
Complications
Hemorrhage may occur as a result of overaggressive therapy.
Rethrombosis may occur as a result of inadequate therapy.
Catastrophic antiphospholipid antibody syndrome can lead to death (50% mortality rate).
Prognosis
The long-term prognosis varies and depends on the tissue damage incurred and the organ system or systems affected. Clinical manifestations that are associated with a worse prognosis include the following: [104, 105, 106]
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Pulmonary hypertension
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Neurologic involvement (eg, CNS involvement, transverse myelopathy)
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Myocardial ischemia
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Nephropathy
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Gangrene of the extremities
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Catastrophic antiphospholipid antibody syndrome
Patient Education
Lifestyle counseling is indicated to educate patients and their families about the risk factors that are known to complicate the prognosis of patients with antiphospholipid antibody syndrome.
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Dietary manipulation is recommended to prevent obesity, hyperlipidemia, and hypertension, starting at a young age, especially in patients with a family history of these problems.
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Dietary manipulation is recommended to decrease consumption of methionine-containing foods that might increase homocysteine levels in patients carrying mutations of the gene that encodes for methylene tetrahydrofolate reductase mutation (MTHFR). Folate deficiencies need to be identified and corrected in these patients to control homocysteine levels.
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Counsel adolescents about the potential risks of smoking tobacco in this setting. Provide smoking cessation programs for patients who already have started smoking.
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In patients with a secondary antiphospholipid antibody syndrome, encourage compliance with medications for control of underlying disease processes, such as vasculitis and systemic lupus erythematosus (SLE).
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Dietary counseling is indicated for patients on oral anticoagulants.
Maintenance of a consistent diet of foods containing vitamin K
Avoidance of foods and herbs with anticoagulant properties
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Counsel patients regarding the risks of oral contraceptive use and the need for alternative methods of contraception.
Current information for patients and their families can be obtained from the excellent Web sites from the St. Thomas Hospital in London (Hughes Syndrome, Hughes Syndrome Foundation).
For excellent patient education resources, visit eMedicineHealth's Brain and Nervous System Center. Also, see eMedicineHealth's patient education articles Blood Clot in the Legs and Stroke.
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Palmar livedo reticularis associated with antiphospholipid antibody syndrome may range from a lacy, flat, reticulated pattern to a more confluent, nonblanching, slightly raised rash (secondary to extravasation of RBCs and plasma).
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Livedo reticularis of the upper and lower extremities in a 15-year-old adolescent with primary antiphospholipid antibody syndrome. The pattern is lacy, flat, and nonblanching. The purplish hue is from stasis in the small vessel beds.
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Muddy discoloration and mild diffuse swelling of the fingers observed as part of the Raynaud phenomenon, which is associated with antiphospholipid antibody syndrome. At room temperature, this patient still has decreased capillary refill and cold fingers despite treatment with pentoxifylline. The discoloration extends proximally onto the palms and turns blue-purple when exposed to cold.
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Linear splinter hemorrhages are found under the nails of fingers and toes. These may be solitary or multiple and appear intermittently.
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One set of suggested algorithms for the workup and treatment of patients with antiphospholipid antibody syndrome. This should not be considered dogmatic because laboratory evaluation is not standardized and treatment remains empiric and controversial. Laboratory testing is not recommended in healthy asymptomatic individuals with no risk factors and a negative family history.
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Occlusion of the right middle cerebral artery in a 3-year-old child with severe headache and hemiparesis associated with anticardiolipin antibodies.
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Organizing thrombus in an aortic valve in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and recurrent thrombotic events. The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
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High-power degenerating aortic valve in a patient who has positive test results for antiphospholipid antibody and lupus anticoagulant and who has systemic lupus erythematosus (SLE) and recurrent thrombotic events. The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
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Trichrome stain of a thrombus in the intestinal serosa in a patient who has positive test results for antiphospholipid antibody and lupus anticoagulant and who has systemic lupus erythematosus (SLE) and catastrophic antiphospholipid antibody syndrome (CAPS). The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessels (periodic acid-Schiff [PAS], original magnification X40). Bottom: Thrombosed kidney vessels (PAS, original magnification X20). Lumen is filled with eosinophilic fibrin with overlying injured endothelial cells. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessel (hematoxylin and eosin [H&E] stain, original magnification X20). Lumen is occluded with fibrin. A perivascular stromal reaction with degenerating inflammatory cells is observed. Bottom: Thrombosed kidney vessel (H&E stain, original magnification X20). Lumen is occluded with fibrin. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Thrombosed kidney vessel with recanalization (arrows) (Jones stain, original magnification X20). Architectural distortion in the surrounding stroma is observed. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and thrombocytopenia. Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern, is observed.
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Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern and evolved as a confluent, nonblanching, slightly raised purpuric rash in the same reticular pattern.
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Digital infarctions in a patient with systemic lupus erythematosus with antiphospholipid syndrome (APS) and long-standing Raynaud symptoms. Multiple and repeated digital infarctions are depicted, resulting in ulcerations and scarring. Scars and hyperpigmentation are also seen on the palmer aspect of hands and fingers.
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A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Extensive involvement of all digits is noted, some with distal infarction and dry gangrene, others healing with residual eschar (and undermining epithelialization), and some with re-epithelialization and scarring. Healed superficial epidermal damage and desquamation is also present.
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A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Eschar is still present on first digit bilaterally. More superficial lesions are shown here, with evolution and healing of lesions on all other toes.
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CAPS, Bone Infarction - MRI (High Resolution Proton Density and STIR images) and Nuclear Bone Scan - Patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. MRI shows multiple infarctions in the distal tibia, tarsal bones and metatarsal bones (extensive bone marrow edema and increased T1 with fat saturation signal in the calcaneus bones). Flow and early blood pool images of technetium 99m bone scan show increase in activity in both heel regions with focal areas of decreased activity in the center of each calcaneus.
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A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. The technetium 99m bone scan reveals irregular multifocal areas of tracer accumulation within the left ventricle of the heart suggestive of myocardial infarction and altered calcium deposition. Irregular cutaneous and subcutaneous uptake is noted in multiple areas of the torso and upper arms (as well as in the upper thighs). High-resolution CT scanning of the chest reveals extensive calcification involving the myocardium, the mitral and tricuspid valve annuli, the aortic valve annulus, the proximal right coronary artery, and the left main coronary artery.
