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.

Warfarin and vitamin K antagonists are anticoagulants that can be taken orally to reduce thromboembolic occurrence. Where a more effective response is required, heparin can be given (by injection) concomitantly. As a side effect of any anticoagulant, the risk of bleeding is increased, so the international normalized ratio of blood is monitored. Self-monitoring and self-management are safe options for competent patients, though their practice varies. In Germany, about 20% of patients were self-managed while only 1% of U.S. patients did home self-testing (according to one 2012 study). Other medications such as direct thrombin inhibitors and direct Xa inhibitors are increasingly being used instead of warfarin.

Thrombolysis is the pharmacological destruction of blood clots by administering thrombolytic drugs including recombitant tissue plasminogen activator, which enhances the normal destruction of blood clots by the body's enzymes. This carries an increased risk of bleeding so is generally only used for specific situations (such as severe stroke or a massive pulmonary embolism).

There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.

Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events, male sex, the presence of an inferior vena cava filter, the presence of cancer, symptoms of post-thrombotic syndrome, and obesity. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia.

Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the antibody titer (amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion.

Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child. Low molecular weight heparin (LMWH, such as enoxaparin) is generally used as an alternative. Warfarin and LMWH may safely be used in breastfeeding.

When women experience recurrent pregnancy loss secondary to thrombophilia, some studies have suggested that low molecular weight heparin reduces the risk of miscarriage. When the results of all studies are analysed together, no statistically signifiant benefit could be demonstrated.

The World Health Organization recommends that women with severe hypertension during pregnancy should receive treatment with anti-hypertensive agents. Severe hypertension is generally considered systolic BP of at least 160 or diastolic BP of at least 110. Evidence does not support the use of one anti-hypertensive over another. The choice of which agent to use should be based on the prescribing clinician's experience with a particular agent, its cost, and its availability. Diuretics are not recommended for prevention of preeclampsia and its complications. Labetolol, Hydralazine and Nifedipine are commonly used antihypertensive agents for hypertension in pregnancy. ACE inhibitors and angiotensin receptor blockers are contraindicated as they affect fetal development.

The goal of treatment of severe hypertension in pregnancy is to prevent cardiovascular, kidney, and cerebrovascular complications. The target blood pressure has been proposed to be 140–160 mmHg systolic and 90–105 mmHg diastolic, although values are variable.

The intrapartum and postpartum administration of magnesium sulfate is recommended in severe pre-eclampsia for the prevention of eclampsia. Further, magnesium sulfate is recommended for the treatment of eclampsia over other anticonvulsants. Magnesium sulfate acts by interacting with NMDA receptors.

Anticoagulation, which prevents further coagulation, but does not act directly on existing clots, is the standard treatment for DVT. Balancing risk vs. benefit is important in determining the duration of anticoagulation, and three months is generally the standard length of treatment. In those with an annual risk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation is a possibility. Those who finish VKA treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs about 4% for normal results), and this result might be used in clinical decision-making. Thrombophilia test results rarely play a role in the length of treatment.

For acute cases in the leg, the ACCP recommended a parenteral anticoagulant (such as LMWH, fondaparinux, or unfractionated heparin) for at least five days and a VKA, the oral anticoagulant, the same day. LMWH and fondaparinux are suggested over unfractionated heparin, but both are retained in those with compromised kidney function, unlike unfractionated heparin. The VKA is generally taken for a minimum of three months to maintain an international normalized ratio of 2.0–3.0, with 2.5 as the target. The benefit of taking a VKA declines as the duration of treatment extends, and the risk of bleeding increases with age.

The ACCP recommended treatment for three months in those with proximal DVT provoked by surgery. A three-month course is also recommended for those with proximal DVT provoked by a transient risk factor, and three months is suggested over lengthened treatment when bleeding risk is low to moderate. Unprovoked DVT patients should have at least three months of anticoagulation and be considered for extended treatment. Those whose first VTE is an unprovoked proximal DVT are suggested for anticoagulation longer than three months unless there is a high risk of bleeding. In that case, three months is sufficient. Those with a second unprovoked VTE are recommended for extended treatment when bleeding risk is low, suggested for extended treatment when bleeding risk is moderate, and suggested for three months of anticoagulation in high-risk scenarios.

The ACCP recommended initial home treatment instead of hospital treatment for those with acute leg DVT. This applies as long as individuals feel ready for it, and those with severe leg symptoms or comorbidities would not qualify. An appropriate home environment is expected: one that can provide a quick return to the hospital if necessary, support from family or friends, and phone access.

In addition to anticoagulation, the ACCP suggested graduated compression stockings—which apply higher pressure (30–40 mm Hg) at the ankles and a lower pressure around the knees—for those with symptomatic DVT. Use should begin as soon as possible after anticoagulation. Evidence however does not support that these stockings reduce the risk of post-thrombotic syndrome nor do they indicate a reduction in recurrent VTE. Use is suggested for two years, though inconvenience and discomfort can reduce compliance. Walking is also suggested for those without severe pain or edema.

Unless a person has medical problems preventing movement, after a person starts anti-coagulation therapy bed rest should not be used to treat acute deep vein thrombosis. There are clinical benefits associated with walking and no evidence that walking is harmful, but people with DVT are harmed by bed rest except when it is medically necessary.

Instead of anticoagulation, a follow-up imaging test (typically ultrasound) about one-week post-diagnosis is an option for those with an acute isolated distal DVT without a high risk for extension; if the clot does not grow, the ACCP does not recommend anticoagulation. This technique can benefit those at a high risk for bleeding. Patients may choose anticoagulation over serial imaging, however, to avoid the inconvenience of another scan if concerns about the risk of bleeding are insignificant. When applied to symptomatic patients with a negative initial ultrasound result, serial testing is inefficient and not cost effective.

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.

As there is no cure, treatment is focused on prevention of thrombotic complications by counseling. In addition, temporary treatment with an anticoagulant may be required during periods of particularly high risk of thrombosis, such as major surgery.

In last decade, similar to myocardial infarction treatment, thrombolytic drugs were introduced in the therapy of cerebral infarction. The use of intravenous rtPA therapy can be advocated in patients who arrive to stroke unit and can be fully evaluated within 3 h of the onset.

If cerebral infarction is caused by a thrombus occluding blood flow to an artery supplying the brain, definitive therapy is aimed at removing the blockage by breaking the clot down (thrombolysis), or by removing it mechanically (thrombectomy). The more rapidly blood flow is restored to the brain, the fewer brain cells die. In increasing numbers of primary stroke centers, pharmacologic thrombolysis with the drug tissue plasminogen activator (tPA), is used to dissolve the clot and unblock the artery.

Another intervention for acute cerebral ischaemia is removal of the offending thrombus directly. This is accomplished by inserting a catheter into the femoral artery, directing it into the cerebral circulation, and deploying a corkscrew-like device to ensnare the clot, which is then withdrawn from the body. Mechanical embolectomy devices have been demonstrated effective at restoring blood flow in patients who were unable to receive thrombolytic drugs or for whom the drugs were ineffective, though no differences have been found between newer and older versions of the devices. The devices have only been tested on patients treated with mechanical clot embolectomy within eight hours of the onset of symptoms.

Angioplasty and stenting have begun to be looked at as possible viable options in treatment of acute cerebral ischaemia. In a systematic review of six uncontrolled, single-center trials, involving a total of 300 patients, of intra-cranial stenting in symptomatic intracranial arterial stenosis, the rate of technical success (reduction to stenosis of <50%) ranged from 90-98%, and the rate of major peri-procedural complications ranged from 4-10%. The rates of restenosis and/or stroke following the treatment were also favorable. This data suggests that a large, randomized controlled trial is needed to more completely evaluate the possible therapeutic advantage of this treatment.

If studies show carotid stenosis, and the patient has residual function in the affected side, carotid endarterectomy (surgical removal of the stenosis) may decrease the risk of recurrence if performed rapidly after cerebral infarction. Carotid endarterectomy is also indicated to decrease the risk of cerebral infarction for symptomatic carotid stenosis (>70 to 80% reduction in diameter).

In tissue losses that are not immediately fatal, the best course of action is to make every effort to restore impairments through physical therapy, cognitive therapy, occupational therapy, speech therapy and exercise.

Treatment of DIC is centered around treating the underlying condition. Transfusions of platelets or fresh frozen plasma can be considered in cases of significant bleeding, or those with a planned invasive procedure. The target goal of such transfusion depends on the clinical situation. Cryoprecipitate can be considered in those with a low fibrinogen level.

Treatment of thrombosis with anticoagulants such as heparin is rarely used due to the risk of bleeding.

Recombinant human activated protein C was previously recommended in those with severe sepsis and DIC, but drotrecogin alfa has been shown to confer no benefit and was withdrawn from the market in 2011.

Recombinant factor VII has been proposed as a "last resort" in those with severe hemorrhage due to obstetric or other causes, but conclusions about its use are still insufficient.

For people who have severe congenital protein C deficiency, protein C replacement therapies are available, which is indicated and approved for use in the United States and Europe for the prevention of purpura fulminans. Protein C replacement is often in combination with anticoagulation therapy of injectable low molecular weight heparin or oral warfarin. Before initiating warfarin therapy, a few days of therapeutic heparin may be administered to prevent warfarin skin necrosis and other progressive or recurrent thrombotic complications.

Early stage sepsis-associated purpura fulminans may be reversible with quick therapeutic intervention. Treatment is mainly removing the underlying cause and degree of clotting abnormalities and with supportive treatment (antibiotics, volume expansion, tissue oxygenation, etc.). Thus, treatment includes aggressive management of the septic state.

Purpura fulminans with disseminated intravascular coagulation should be urgently treated with fresh frozen plasma (10–20 mL/kg every 8–12 hours) and/or protein C concentrate to replace pro-coagulant and anticoagulant plasma proteins that have been depleted by the disseminated intravascular coagulation process.

Protein C in plasma in the steady state has a half life of 6- to 10-hour, therefore, patients with severe protein C deficiency and presenting with purpura fulminans can be treated acutely with an initial bolus of protein C concentrate 100 IU/kg followed by 50 IU /kg every 6 hours. A total of 1 IU/kg of protein C concentrate or 1 mL/kg of fresh frozen plasma will increase the plasma concentration of protein C by 1 IU/dL. Cases with comorbid pathological bleeding may require additional transfusions with platelet concentrate (10–15 mL/kg) or cryoprecipitate (5 mL/kg).

Established soft tissue necrosis may require surgical removal of the dead tissue, fasciotomy, amputation or reconstructive surgery.

Due to the high mortality of untreated TTP, a presumptive diagnosis of TTP is made even when only microangiopathic hemolytic anemia and thrombocytopenia are seen, and therapy is started. Transfusion is contraindicated in thrombotic TTP, as it fuels the coagulopathy. Since the early 1990s, plasmapheresis has become the treatment of choice for TTP. This is an exchange transfusion involving removal of the patient's blood plasma through apheresis and replacement with donor plasma (fresh frozen plasma or cryosupernatant); the procedure must be repeated daily to eliminate the inhibitor and abate the symptoms. If apheresis is not available, fresh frozen plasma can be infused, but the volume that can be given safely is limited due to the danger of fluid overload. Plasma infusion alone is not as beneficial as plasma exchange. Corticosteroids (prednisone or prednisolone) are usually given. Rituximab, a monoclonal antibody aimed at the CD20 molecule on B lymphocytes, may be used on diagnosis; this is thought to kill the B cells and thereby reduce the production of the inhibitor. A stronger recommendation for rituximab exists where TTP does not respond to corticosteroids and plasmapheresis.

Caplacizumab is an alternative option in treating TTP as it has been shown that it induces a faster disease resolution compared with those patient who were on placebo. However, the use of caplacizumab was associated with increase bleeding tendencies in the studied subjects.

Most patients with refractory or relapsing TTP receive additional immunosuppressive therapy, e.g. vincristine, cyclophosphamide, splenectomy or a combination of the above.

Children with Upshaw-Schülman syndrome receive prophylactic plasma every two to three weeks; this maintains adequate levels of functioning ADAMTS13. Some tolerate longer intervals between plasma infusions. Additional plasma infusions may necessary for triggering events, such as surgery; alternatively, the platelet count may be monitored closely around these events with plasma being administered if the count drops.

Measurements of blood levels of lactate dehydrogenase, platelets, and schistocytes are used to monitor disease progression or remission. ADAMTS13 activity and inhibitor levels may be measured during follow-up, but in those without symptoms the use of rituximab is not recommended.

Management of the underlying defect is proportional to the severity of the clinical presentation. Leg swelling and pain is best evaluated by vascular specialists (vascular surgeons, interventional cardiologists, interventional radiologists) who both diagnose and treat arterial and venous diseases to ensure that the cause of the extremity pain is evaluated. The diagnosis needs to be confirmed with some sort of imaging that may include magnetic resonance venography, venogram and usually confirmed with intravascular ultrasound because the flattened vein may not be noticed on conventional venography. In order to prevent prolonged swelling or pain from the consequences of the backed up blood from the compressed iliac vein, flow needs to be improved out of the leg. Uncomplicated cases may be managed with compression stockings.

Severe May-Thurner syndrome may require thrombolysis if there is a recent onset of thrombosis, followed by angioplasty and stenting of the iliac vein after confirming the diagnosis with a venogram or an intravascular ultrasound. A stent may be used to support the area from further compression following angioplasty. As the name implies, there classically is not a thrombotic component in these cases, but thrombosis may occur at any time.

If the patient has extensive thrombosis, it may be appropriate to consider pharmacologic and/or mechanical (also known as pharmacomechanical) thrombectomy. This is currently being studied to determine whether this will decrease the incidence of post-thrombotic syndrome.

It can be diagnosed by histomorphologic examination of the placenta and is characterized by fetal vessel thrombosis and clustered fibrotic chorionic villi without blood vessels.

Fetal thrombotic vasculopathy is a chronic disorder characterized by thrombosis in the fetus leading to vascular obliteration and hypoperfusion.

It is associated with cerebral palsy and stillbirth.

If ongoing and rapid haemorrhage is occurring then immediate delivery of the foetus may be indicated if the fetus is sufficiently developed. If the haemorrhage has already occurred and now stopped, an inutero transfusion of red cells to the foetus may be recommended.

The treatment depends on the cause.

Severely anemic fetuses, including those with Rh disease and alpha thalassemia major, can be treated with blood transfusions while still in the womb. This treatment increases the chance that the fetus will survive until birth.

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.

Individuals with hypofibrinogenemia who have a history of excessive bleeding should be treated at a center specialized in treating hemophilia and avoid all medications that interfere with normal platelet function. During bleeding episodes, treatment with fibrinogen concentrates or, if unavailable infusion of fresh frozen plasma and/or cryoprecipitate (a fibrinogen-rich plasma fraction) to maintain fibrinogen activity levels >1 gram/liter.

Individuals with hypofibrinogenemia who experience episodic thrombosis should also be treated at a center specialized in treating hemophilia. Standard recommendations for these individuals are that they use antithrombotic agents and be instructed on antithrombotic behavioral methods in high risk situations (e.g. long car rides and air flights]]. Acute venous thrombosis episodes should be treated with low molecular weight heparin for a time that depends on personal and family history of thrombosis events. Prophylactic treatment prior to minor surgery should avoid fibrinogen supplementation and use anticoagulation measures; prior to major surgery, fibrinogen supplementation should be used only if serious bleeding occurs; otherwise, prophylactic anticoagulation measures are recommended.

The management of lipodermatosclerosis may include treating venous insufficiency with leg elevation and elastic compression stockings; in some difficult cases, the condition may be improved with the additional use of the fibrinolytic agent, stanozol. Fibrinolytic agents use an enzymatic action to help dissolve blood clots.

Stanozol is injected directly into the affected area, Venous Ablation has also been known to help circulation in patients.

There are too few cases of fibrinogen storage disease to establish optimal treatments for the liver diseases. Management of the disorder has been based on general recommendations for patients with liver disease, particularly Alpha 1 antitrypsin deficiency-associated liver disease. In the latter disease, autophagy, the pathway that cells use to dispose of dysfunctional or excessively stored components including proteins, has been targeted using autophagy-enhancing drugs, e.g. carbamazepine, vitamin E, and ursodeoxycholic acid. These drugs have been tested in individual patients with fibrin storage disease with some success in reducing evidence of liver injure, i.e. reduction in blood liver enzyme levels. These and other autophagy-enhancing drugs are suggested to be further studied in fibrinogen storage disease.

The optimal treatment is prevention. Rigorous and continuous control of phosphate and calcium balance most probably will avoid the metabolic changes which may lead to calciphylaxis.

There is no specific treatment. Of the treatments that exist, none are internationally recognized as the standard of care. An acceptable treatment could include:

- Dialysis (the number of sessions may be increased)

- Intensive wound care

- Clot-dissolving agents (tissue plasminogen activator)

- Hyperbaric oxygen

- Maggot larval debridement

- Adequate pain control

- Correction of the underlying plasma calcium and phosphorus abnormalities (lowering the Ca x P product below 55 mg2/dL2)

- Sodium thiosulfate

- Avoiding (further) local tissue trauma (including avoiding all subcutaneous injections, and all not-absolutely-necessary infusions and transfusions)

- Urgent parathyroidectomy: The efficacy of this measure remains uncertain although calciphylaxis is associated with frank hyperparathyroidism. Urgent parathyroidectomy may benefit those patients who have uncontrollable plasma calcium and phosphorus concentrations despite dialysis. Also, cinacalcet can be used and may serve as an alternative to parathyroidectomy.

- Patients who receive kidney transplants also receive immunosuppression. Considering lowering the dose of or discontinuing the use of immunosuppressive drugs in people who have received kidney transplants and continue to have persistent or progressive calciphylactic skin lesions can contribute to an acceptable treatment of calciphylaxis.

- A group has reported plasma exchange effective and propose a serum marker and perhaps mediator (calciprotein particles)