Antiphospholipid syndrome is tested for in the laboratory using both liquid phase coagulation assays (lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies).

Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus genetic thrombophilia screening can consist of:

- Further studies for factor V Leiden variant and the prothrombin G20210A mutation, factor VIII levels, MTHFR mutation.

- Levels of protein C, free and total protein S, factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)

The testing of antibodies to the possible individual targets of aPL such as β glycoprotein 1 and antiphosphatidyl serine is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though cardiolipin is not considered an in vivo target for antiphospholipid antibodies.

Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of βglycoprotein 1 dependent anticardiolipin antibodies (ACA).

A low platelet count and positivity for antibodies against β-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis.

There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the hepatic vein in Budd-Chiari syndrome), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis. In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventative treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent orthopedic surgery, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results.

When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patient's indicated treatment. In 2013, the American Society of Hematology, as part of recommendations in the Choosing Wisely campaign, cautioned against overuse of thrombophilia screening; false positive results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical need

In the United Kingdom, professional guidelines give specific indications for thrombophilia testing. It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In particular situations, such as retinal vein thrombosis, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as evidence-based. If cost-effectiveness (quality-adjusted life years in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.

Recurrent miscarriage is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as thromboelastography.

Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has suffered from thrombosis, the risk of developing thrombosis is increased. Screening this selected group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.

Thrombophilia screening in people with arterial thrombosis is generally regarded unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by smoking or use of estrogen-containing hormonal contraceptives) and those in whom revascularization, such as coronary arterial bypass, fails because of rapid occlusion of the graft.

Tests for thrombophilia include complete blood count (with examination of the blood film), prothrombin time, partial thromboplastin time, thrombodynamics test, thrombin time and reptilase time, lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein 1 antibody, activated protein C resistance, fibrinogen tests, factor V Leiden and prothrombin mutation, and basal homocysteine levels. Testing may be more or less extensive depending on clinical judgement and abnormalities detected on initial evaluation.

For hereditary cases, the patient must have at least 2 abnormal tests plus family history.

Treatment for a lupus anticoagulant is usually undertaken in the context of documented thrombosis, such as extremity phlebitis or dural sinus vein thrombosis. Patients with a well-documented (i.e., present at least twice) lupus anticoagulant and a history of thrombosis should be considered candidates for indefinite treatment with anticoagulants. Patients with no history of thrombosis and a lupus anticoagulant should probably be observed. Current evidence suggests that the risk of recurrent thrombosis in patients with an antiphospholipid antibody is enhanced whether that antibody is measured on serological testing or functional testing. The Sapporo criteria specify that both serological and functional tests must be positive to diagnose the antiphospholipid antibody syndrome.

Miscarriages may be more prevalent in patients with a lupus anticoagulant. Some of these miscarriages may "potentially" be prevented with the administration of aspirin and unfractionated heparin. The Cochrane Database of Systematic Reviews provide a deeper understanding on the subject.

Thrombosis is treated with anticoagulants (LMWHs and warfarin).

The presence of prolonged clotting times on a routine plasma test often triggers functional testing of the blood clotting function, as well as serological testing to identify common autoantibodies such as antiphospholipid antibodies. These antibodies tend to delay in-vitro coagulation in phospholipid-dependent laboratory tests such as the partial thromboplastin time.

The initial workup of a prolonged PTT is a mixing test whereby the patient's plasma is mixed with normal pooled plasma and the clotting is re-assessed. If a clotting inhibitor such as a lupus anticoagulant is present, the inhibitor will interact with the normal pooled plasma and the clotting time will remain abnormal. However, if the clotting time of the mixed plasma corrects towards normal, the diagnosis of an inhibitor such as the lupus anticoagulant is excluded; the diagnosis is a deficient quantity of clotting factor that is replenished by the normal plasma.

If the mixing test indicates an inhibitor, diagnosis of a lupus anticoagulant is then confirmed with phospholipid-sensitive functional clotting testing, such as the dilute Russell's viper venom time, or the Kaolin clotting time. Excess phospholipid will eventually correct the prolongation of these prolonged clotting tests (conceptually known as "phospholipid neutralization" in the clinical coagulation laboratory), confirming the diagnosis of a lupus anticoagulant.

There are no diagnostic tests on which all Sneddon's patients will have abnormal results, although brain MRI and skin biopsy are often abnormal. The diagnosis is based on a detailed history and physical examination. About 40-60% of patients with the syndrome test positive for antiphospholipid antibodies.

CBC and blood film: decreased platelets and schistocytes PT, aPTT, fibrinogen: normal Markers of hemolysis: increased unconjugated bilirubin, increased LDH, decreased haptoglobin Negative Coombs test

Creatinine, urea, to follow renal function ADAMSTS-13 gene, activity or inhibitor testing (TTP)

In terms of treatment for protein S deficiency the following are consistent with the "management" (and administration of) individuals with this condition ( it should be noted that the prognosis for "inherited" homozygotes is usually in line with a higher incidence of thrombosis for the affected individual):

In general, the indications for anticoagulation during pregnancy are the same as the general population. This includes (but is not limited to) a recent history of deep venous thrombosis (DVT) or pulmonary embolism, a metallic prosthetic heart valve, and atrial fibrillation in the setting of structural heart disease.

In addition to these indications, anticoagulation may be of benefit in individuals with lupus erythematosus, individuals who have a history of DVT or PE associated with a previous pregnancy, and even with individuals with a history of coagulation factor deficiencies and DVT not associated with a previous pregnancy.

In pregnant women with a history of recurrent miscarriage, anticoagulation seems to increase the live birth rate among those with antiphospholipid syndrome and perhaps those with congenital thrombophilia but not in those with unexplained recurrent miscarriage.

Sneddon's patients are generally treated with warfarin, maintaining a high INR of 3-4. Because most will experience significant relief of symptoms after several months of consistent INR in this range, treatment with warfarin is often used as a diagnostic tool.

The diagnosis for deficiency of protein S can be done via reviewing family history of condition and genetic testing, as well as the following:

- Protein S antigen test

- Coagulation test (prothrombin time test)

- Thrombotic disease investigation

- Factor V Leiden test

When Budd–Chiari syndrome is suspected, measurements are made of liver enzyme levels and other organ markers (creatinine, urea, electrolytes, LDH).

Budd–Chiari syndrome is most commonly diagnosed using ultrasound studies of the abdomen and retrograde angiography. Ultrasound may show obliteration of hepatic veins, thrombosis or stenosis, spiderweb vessels, large collateral vessels, or a hyperechoic cord replacing a normal vein. Computed tomography (CT) or magnetic resonance imaging (MRI) is sometimes employed although these methods are generally not as sensitive. Liver biopsy is nonspecific but sometimes necessary to differentiate between Budd–Chiari syndrome and other causes of hepatomegaly and ascites, such as galactosemia or Reye's syndrome.

A detailed history is important to elicit any recent medications, any risk of hepatitis infection, or any recent diagnosis with a connective tissue disorder such as systemic lupus erythematosus (SLE). A thorough physical exam is needed as usual.

- Lab tests. Basic lab tests may include a CBC, chem-7 (look for creatinine), muscle enzyme, liver function tests, ESR, hepatitis seroloties, urinalysis, CXR, and EKG. Additional, more specific tests include:

- Antinuclear antibody (ANA) test can detect an underlying connective tissue disorder, especially SLE

- Complement levels that are low can suggest mixed cryoglobulinemia, hepatitis C infection, and SLE, but not most other vasculitides.

- Antineutrophil cytoplasmic antibody (ANCA) may highly suggest granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, or drug-induced vasculitis, but is not diagnostic.

- Electromyography. It is useful if a systemic vasculitis is suspected and neuromuscular symptoms are present.

- Arteriography. Arteriograms are helpful in vasculitis affecting the large and medium vessels but not helpful in small vessel vasculitis. Angiograms of mesenteri or renal arteries in polyarteritis nodosa may show aneurysms, occlusions, and vascular wall abnormalities. Arteriography are not diagnostic in itself if other accessible areas for biopsy are present. However, in Takayasu's arteritis, where the aorta may be involved, it is unlikely a biopsy will be successful and angiography can be diagnostic.

- Tissue biopsy. This is the gold standard of diagnosis when biopsy is taken from the most involved area.

There are no laboratory tests used to diagnose RVT.

Observing the patient's symptoms, medical history and imaging remain the fundamental source for diagnosing RVT. Imaging is used to detect the presence of a blood clot. In an abnormal kidney with RVT, a blood clot is present in the renal vein. In cases where the renal vein is suddenly and/or fully blocked, the kidneys will enlarge, reaching its maximum size within a week. An ultrasound imaging can be used to observe and track the size of the kidneys in RVT patients. Ultrasound is not efficient for use in detecting blood flow in the renal veins and artery. Instead a color doppler ultrasound may be used to detect renal blood flow. It is most commonly used to detect RVT in patients who have undergone renal transplantation. CT angiography is currently the top choice in diagnosing RVT. It is non-invasive, relatively cheap and fast with high accuracy. CT scanning can be used to detect renal enlargement, renal tumors, blood flow and other renal pathologies. An alternative is magnetic resonance angiography or MRA. It is non-invasive, fast and avoids radiation (unlike a CT scan) but it is relatively expensive. MRA produces detailed images of the renal blood flow, vesicle walls, the kidneys and any surrounding tissue. An inferior venocavography with selective venography can be used to rule out the diagnoses of RVT.

A diagnosis of TTP is based on the clinical symptoms with the concomitant presence of thrombocytopenia (platelet count below 100×10/L) and microangiopathic hemolytic anemia with schistocytes on the blood smear, a negative direct antiglobulin test (coombs test), elevated levels of hemolysis markers (such as total bilirubin, LDH, free hemoglobin and an unmeasurable haptoglobin), after exclusion of any other apparent cause.

USS can present similar to the following diseases which have to be excluded: fulminant infections, disseminated intravascular coagulation, autoimmune hemolytic anemia, Evans syndrome, the typical and atypical form of hemolytic uremic syndrome (HUS), HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, pre-eclampsia, heparin-induced thrombocytopenia (HIT), cancer that is often accompanied with metastasis, kidney injury, antiphospholipid antibody syndrome and side effects from hematopoietic stem cell transplantation.

Of note is that pregnancy associated affections like pre-eclampsia, eclampsia and HELLP syndrome can overlap in their presentation as pregnancy can trigger TTP episodes.

Patients with fulminant infections, disseminated intravascular coagulation, HELLP syndrome, pancreatitis, liver disease and other active inflammatory conditions may have reduced ADAMTS13 activity but almost never a relevant severe ADAMTS13 deficiency <10% of the normal.

A severe ADAMTS13 deficiency below 5% or <10% of the normal (depending on the definitions) is highly specific for the diagnosis of TTP. ADAMTS13 activity assays are based on the direct or indirect measurement of VWF-cleavage products. Its activity should be measured in blood samples taken before therapy has started, to prevent false high ADAMTS13 activity. If a severe ADAMTS13 deficiency is present an ADAMTS13 inhibitor assay is needed to distinguish between the acquired, autoantibody-mediated and the congenital form of TTP (USS). The presence of antibodies can be tested by ELISA or functional inhibitor assays. The level of ADAMTS13 inhibitor may be fluctuating over the course of disease and depends on free circulatory antibodies, therefore an onetime negative test result does not always exclude the presence of ADAMTS13 inhibitors and thereby an autoimmune origin of TTP. A severe ADAMTS13 deficiency in the absence of an inhibitor, confirmed on a second time point in a healthy episode of a possible USS patient, usually sets the trigger to perform a molecular analysis of the "ADAMTS13" gene to confirm a mutation. In unclear cases a plasma infusion trial can be done, showing an USS in the absence of anti-ADAMTS13-antibodies a full recovery of infused plasma-ADAMTS13 activity as well as a plasma half-life of infused ADAMTS13 activity of 2–4 days. A deficiency of ADAMTS13 activity in first-degree relatives is also a very strong indicator for an Upshaw-Schulman Syndrome.

The course of treatment and the success rate is dependent on the type of TMA. Some patients with atypical HUS and TTP have responded to plasma infusions or exchanges, a procedure which replaces proteins necessary for the complement cascade that the patient does not have; however, this is not a permanent solution or treatment, especially for patients with congenital predispositions.

Some physicians make a diagnosis on the basis of the American College of Rheumatology (ACR) classification criteria. The criteria, however, were established mainly for use in scientific research including use in randomized controlled trials which require higher confidence levels, so many people with SLE may not pass the full criteria.

Several studies have attempted to predict the survival of patients with Budd–Chiari syndrome. In general, nearly 2/3 of patients with Budd–Chiari are alive at 10 years. Important negative prognostic indicators include ascites, encephalopathy, elevated Child-Pugh scores, elevated prothrombin time, and altered serum levels of various substances (sodium, creatinine, albumin, and bilirubin). Survival is also highly dependent on the underlying cause of the Budd–Chiari syndrome. For example, a patient with an underlying myeloproliferative disorder may progress to acute leukemia, independently of Budd–Chiari syndrome.

Antinuclear antibody (ANA) testing and anti-extractable nuclear antigen (anti-ENA) form the mainstay of serologic testing for SLE. Several techniques are used to detect ANAs. Clinically the most widely used method is indirect immunofluorescence (IF). The pattern of fluorescence suggests the type of antibody present in the people's serum. Direct immunofluorescence can detect deposits of immunoglobulins and complement proteins in the people's skin. When skin not exposed to the sun is tested, a positive direct IF (the so-called lupus band test) is an evidence of systemic lupus erythematosus.

ANA screening yields positive results in many connective tissue disorders and other autoimmune diseases, and may occur in normal individuals. Subtypes of antinuclear antibodies include anti-Smith and anti-double stranded DNA (dsDNA) antibodies (which are linked to SLE) and anti-histone antibodies (which are linked to drug-induced lupus). Anti-dsDNA antibodies are highly specific for SLE; they are present in 70% of cases, whereas they appear in only 0.5% of people without SLE. The anti-dsDNA antibody titers also tend to reflect disease activity, although not in all cases. Other ANA that may occur in people with SLE are anti-U1 RNP (which also appears in systemic sclerosis and mixed connective tissue disease), SS-A (or anti-Ro) and SS-B (or anti-La; both of which are more common in Sjögren's syndrome). SS-A and SS-B confer a specific risk for heart conduction block in neonatal lupus.

Other tests routinely performed in suspected SLE are complement system levels (low levels suggest consumption by the immune system), electrolytes and kidney function (disturbed if the kidney is involved), liver enzymes, and complete blood count.

The lupus erythematosus (LE) cell test was commonly used for diagnosis, but it is no longer used because the LE cells are only found in 50–75% of SLE cases, and they are also found in some people with rheumatoid arthritis, scleroderma, and drug sensitivities. Because of this, the LE cell test is now performed only rarely and is mostly of historical significance.

Prevention of DVT and other types of venous thrombosis may be required if certain predisposing risk factors are present. One example from Sweden is based on the point system below, where points are summed to give the appropriate prophylaxis regimen.

After adding any risk factors together, a total of one point or less indicates no preventive action is needed. A total of two points indicates short-term prophylaxis, e.g. with LMWH, may be used in temporary risk factors, as well as administering prophylactic treatment seven days postpartum, starting a couple of hours after birth. A total of 3 points increases the necessary duration of "post partum" prophylaxis to six weeks.

A risk score of four points or higher means prophylaxis in the "ante partum" period is needed, as well as at least six weeks "post partum". A previous distal DVT indicates a minimum of 12 weeks (three months) of therapeutic anticoagulation therapy. A previous proximal DVT or pulmonary embolism requires a minimum of 26 weeks (6.5 months) of therapy If the therapy duration reaches delivery time, the remaining duration may be given after delivery, possibly extending the minimum of six weeks of "post partum" therapy. In a very high risk, high-dose "ante partum" prophylaxis should be continued at least 12 weeks after delivery.

Women with antiphospholipid syndrome should have an additional low-dose prophylactic treatment of aspirin.

In the presence of suspicious symptoms a number of test are helpful in the diagnosis:

- Muscle enzymes are often elevated, i.e. creatine kinase

- Anti-Jo-1 antibody testing

- Electromyography

- Muscle biopsy

- Pulmonary function testing

- Lung biopsy

In certain situations, testing of other antibodies, specific imaging (MRI, thoracic high resolution computed tomography), and swallowing evaluation may be needed.

Treatment for Thrombotic Storm may include lifelong anticoagulation therapy and/or thrombolytic therapy, plasmapherisis, and corticosteroids. Studies have shown that when anticoagulant therapy is withheld recurrence of thrombosis usually follows. INR is closely monitored in the course of treatment.

In this table: ANA = Antinuclear antibodies, CRP = C-reactive protein, ESR = Erythrocyte Sedimentation Rate, "ds"DNA = double-stranded DNA, ENA = extractable nuclear antigens, RNP = ribonucleoproteins; VDRL = Venereal Disease Research Laboratory

It is known that diabetes causes changes to factors associated with coagulation and clotting, however not much is known of the risk of thromboembolism, or clots, in diabetic patients. There are some studies that show that diabetes increases the risk of thromboembolism; other studies show that diabetes does not increase the risk of thromboembolism. A study conducted in the Umea University Hospital, in Sweden, observed patients that were hospitalized due to an thromboembolism from 1997 to 1999. The researchers had access to patient information including age, sex, vein thromboembolism diagnosis, diagnostic methods, diabetes type and medical history. This study concluded that there is, in fact, an increased risk of thromboembolism development in diabetic patients, possibly due to factors associated with diabetes or diabetes itself. Diabetic patients are twice as likely to develop a thromboembolism than are non-diabetic patient. The exact mechanism of how diabetes increases the risk of clot formation remains unclear and could possibly be a future direction for study.

From previous studies, it is known that long distance air travel is associated with high risk of venous thrombosis. Long periods of inactivity in a limited amount of space may be a reason for the increased risk of blood clot formation. In addition, bent knees compresses the vein behind the knee (the popliteal vein) and the low humidity, low oxygen, high cabin pressure and consumption of alcohol concentrate the blood. A recent study, published in the British Journal of Haematology in 2014, determined which groups of people, are most at risk for developing a clot during or after a long flight. The study focused on 8755 frequent flying employees from international companies and organizations. It found that travelers who have recently undergone a surgical procedure or who have a malignant disease such as cancer or who are pregnant are most at risk. Preventative measures before flying may be taken in these at-risk groups as a solution.

Patients who have undergone kidney transplant have a high risk of developing RVT (about 0.4% to 6%). RVT is known to account for a large proportion of transplanted kidney failures due to technical problems (damage to the renal vein), clotting disorders, diabetes, consumption of ciclosporin or an unknown problem. Patients who have undergone a kidney transplant are commonly prescribed ciclosporin, an immunosuppressant drug which is known to reduce renal blood flow, increase platelet aggregation in the blood and cause damage to the endothelial tissue of the veins. In a clinical study conducted by the Nuffield Department of Surgery at the Oxford Transplant Centre, UK, transplant patients were given low doses of aspirin, which has a some anti-platelet activity. There is risk of bleeding in transplant patients when using anticoagulants like warfarin and herapin. Low dosage of aspirin was used as an alternative. The study concluded that a routine low-dose of aspirin in kidney transplant patients who are also taking ciclosporin significantly reduces the risk of RVT development.