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.

Recommendations for those without cancer include anticoagulation (stopping further blood clots from forming) with dabigatran, rivaroxaban, apixaban, or edoxaban rather than warfarin or low molecular weight heparin (LMWH). For those with cancer LMWH is recommended. For initial treatment of VTE, fixed doses with LMWH may be more effective than adjusted doses of unfractionated heparin (UFH) in reducing blood clots. No differences in mortality, prevention of major bleeding, or preventing VTEs from recurring were observed between LMWH and UFH. No differences have been detected in the route of administration of UFH (subcutaneous or intravenous). LMWH is usually administered by a subcutaneous injection, and a persons blood clotting factors do not have to be monitored as closely as with UFH. People with cancer have a higher risk of experiencing reoccurring VTE episodes ("recurrent VTE"), despite taking preventative anticoagulation medication. These people should be given therapeutic doses of LMWH medication, either by switching from another anticoagulant or by taking a higher dose of LMWH.

For those with a small pulmonary embolism and few risk factors, no anticoagulation is needed. Anticoagulation is; however, recommended in those who do have risk factors. Thrombolysis is recommended in those with PEs that are causing low blood pressure.

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).

Evidence-based clinical guidelines were published in 2016 for the treatment of VTE.

Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded. Clinical practice guidelines now recommend heparin or low molecular weight heparin in the initial treatment, followed by warfarin, provided there are no other bleeding risks that would make these treatments unsuitable. Some experts discourage the use of anticoagulation if there is extensive hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If the hemorrhage has decreased in size, anticoagulants are started, while no anticoagulants are given if there is no reduction.

The duration of warfarin treatment depends on the circumstances and underlying causes of the condition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), three months are regarded as sufficient. If the condition was unprovoked but there are no clear causes or a "mild" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlying thrombosis disorder, warfarin treatment may need to continue indefinitely.

Thrombolysis (removal of the blood clot with "clot buster" medication) has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 European Federation of Neurological Societies guideline recommends that thrombolysis is only used in patients who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis. American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed.

Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), medication (acetazolamide), or neurosurgical treatment (optic nerve sheath fenestration or shunting). In certain situations, anticonvulsants may be used to try to prevent seizures. These situations include focal neurological problems (e.g. inability to move a limb) and focal changes of the brain tissue on CT or MRI scan. Evidence to support or refute the use of antiepileptic drugs as a preventive measure, however, is lacking.

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.

Treatment is aimed at controlling symptoms and improving the interrupted blood flow to the affected area of the body.

Medications include:

- Antithrombotic medication. These are commonly given because thromboembolism is the major cause of arterial embolism. Examples are:

- Anticoagulants (such as warfarin or heparin) and antiplatelet medication (such as aspirin, ticlopidine, and clopidogrel) can prevent new clots from forming

- Thrombolytics (such as streptokinase) can dissolve clots

- Painkillers given intravenously

- Vasodilators to relax and dilate blood vessels.

Appropriate drug treatments successfully produces thrombolysis and removal of the clot in 50% to 80% of all cases.

Antithrombotic agents may be administered directly onto the clot in the vessel using a flexible catheter ("intra-arterial thrombolysis"). Intra-arterial thrombolysis reduces thromboembolic occlusion by 95% in 50% of cases, and restores adequate blood flow in 50% to 80% of cases.

Surgical procedures include:

- Arterial bypass surgery to create another source of blood supply

- Embolectomy, to remove the embolus, with various techniques available:

- Thromboaspiration

- Angioplasty with balloon catheterization with or without implanting a stent Balloon catheterization or open embolectomy surgery reduces mortality by nearly 50% and the need for limb amputation by approximately 35%.

- Embolectomy by open surgery on the artery

If extensive necrosis and gangrene has set in an arm or leg, the limb may have to be amputated. Limb amputation is in itself usually remarkably well tolerated, but is associated with a substantial mortality (~50%), primarily because of the severity of the diseases in patients where it is indicated.

Treatment with compression stockings should be offered to patients with lower extremity superficial phlebitis, if not contraindicated (e.g., peripheral artery disease). Patients may find them helpful for reducing swelling and pain once the acute inflammation subsides.

Nonsteroidal anti-inflammatory drugs (NSAID) are effective in relieving the pain associated with venous inflammation and were found in a randomized trial to significantly decrease extension and/or recurrence of superficial vein thrombosis.

Anticoagulation for patients with lower extremity superficial thrombophlebitis at increased risk for thromboembolism (affected venous segment of ≥5 cm, in proximity to deep venous system, positive medical risk factors).

Treatment with fondaparinux reduces the risk of subsequent venous thromboembolism.

Surgery reserved for extension of the clot to within 1 cm of the saphenofemoral junction in patients deemed unreliable for anticoagulation, failure of anticoagulation and patients with intense pain. Surgical therapy with ligation of saphenofemoral junction or stripping of thrombosed superficial veins appears to be associated higher rates of venous thromboembolism compared with treatment with anitcoagulants.

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.

How well a patient does depends on the location of the clot and to what extent the clot has blocked blood flow. Arterial embolism can be serious if not treated promptly.

Without treatment, it has a 25% to 30% mortality rate. The affected area can be permanently damaged, and up to approximately 25% of cases require amputation of an affected extremity.

Arterial emboli may recur even after successful treatment.

Treatments include anticoagulants, shunts, bypass surgery, and transplants.

Those unsuitable for surgery may receive thrombolytics. In the past, streptokinase was the main thrombolytic chemical. More recently, drugs such as tissue plasminogen activator, urokinase, and anisterplase have been used in its place. Mechanical methods of injecting the thrombolytic compounds have improved with the introduction of pulsed spray catheters—which allow for a greater opportunity for patients to avoid surgery. Pharmacological thrombolysis requires a catheter insert into the affected area, attached to the catheter is often a wire with holes to allow for a wider dispersal area of the thrombolytic agent. These agents lyse the ischemia-causing thrombus quickly and effectively. However, the efficacy of thrombolytic treatment is limited by hemorrhagic complications. Plasma fibrinogen level has been proposed as a predictor of these hemorrhagic complications. However, based on a systemtic review of the available literature until January 2016, the predictive value of plasma is unproven.

The primary intervention in acute limb ischaemia is emergency embolectomy using a Fogarty Catheter, providing the limb is still viable within the 4-6h timeframe. Other options include a vascular bypass to route blood flow around the clot.

Preventing the development of blood clots in the upper extremities is done by accessing the risk of the development of such clots.The traditional treatment for thrombosis is the same as for a lower extremity DVT, and involves systemic anticoagulation to prevent a pulmonary embolus. Some have also recommended thrombolysis with catheter directed alteplase. If there is thoracic outlet syndrome or other anatomical cause then surgery can be considered to correct the underlying defect.

Protamine reverses the effect of unfractionated heparin, but only partially binds to and reverses LMWH. A dose of 1 mg protamine / 100 IU LMWH reverses 90% of its anti-IIa and 60% of anti-Xa activity, but the clinical effect of the residual anti-Xa activity is not known. Both anti-IIa and anti-Xa activity may return up to three hours after protamine reversal, possibly due to release of additional LMWH from depot tissues.

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.

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.

Anticoagulant therapy with LMWH is not usually monitored. LMWH therapy does not affect the prothrombin time (PT) or the INR, and anti-Xa levels are not reliable. It can prolong the partial thromboplastin time (APTT) in some women, but still, the APTT is not useful for monitoring.

To check for any thrombocytopenia, platelet count should be checked prior to commencing anticoagulant therapy, then seven to 10 days after commencement, and monthly thereafter. Platelet count should also be checked if unexpected bruising or bleeding occurs.

Treatment usually consists of NSAIDs, such as ibuprofen and local compression (e.g., by compression stockings or a compress). If the phlebitis is associated with local bacterial infection, antibiotics may be used.

For acute infusion superficial thrombophlebitis, not enough evidence exists as of 2015 to determine treatment.

The mainstay of treatment for CCF is endovascular therapy. This may be transarterial (mostly in the case of direct CCF) or transvenous (most commonly in indirect CCF). Occasionally, more direct approaches, such as direct transorbital puncture of the cavernous sinus or cannulation of the draining superior orbital vein are used when conventional approaches are not possible. Spontaneous resolution of indirect fistulae has been reported but is uncommon. Staged manual compression of the ipsilateral carotid has been reported to assist with spontaneous closure in selected cases.

Direct CCF may be treated by occlusion of the affected cavernous sinus (coils, balloon, liquid agents), or by reconstruction of the damaged internal carotid artery (stent, coils or liquid agents).

Indirect CCF may be treated by occlusion of the affected cavernous sinus with coils, liquid agents or a combination of both.

Given the fact that HIT predisposes strongly to new episodes of thrombosis, it is not sufficient to simply discontinue the heparin administration. Generally, an alternative anticoagulant is needed to suppress the thrombotic tendency while the generation of antibodies stops and the platelet count recovers. To make matters more complicated, the other most commonly used anticoagulant, warfarin, should not be used in HIT until the platelet count is at least 150 x 10^9/L because there is a very high risk of warfarin necrosis in people with HIT who have low platelet counts. Warfarin necrosis is the development of skin gangrene in those receiving warfarin or a similar vitamin K inhibitor. If the patient was receiving warfarin at the time when HIT is diagnosed, the activity of warfarin is reversed with vitamin K. Transfusing platelets is discouraged, as there is a theoretical risk that this may worsen the risk of thrombosis; the platelet count is rarely low enough to be the principal cause of significant hemorrhage.

Various non-heparin agents are used to provide anticoagulation in those with strongly suspected or proven HIT: danaparoid, fondaparinux, bivalirudin and argatroban. These are alternatives to heparin therapy. Not all agents are available in all countries, and not all are approved for this specific use. For instance, argatroban is only recently licensed in the United Kingdom, and danaparoid is not available in the United States. Fondaparinux, a Factor Xa inhibitor, is commonly used off label for HIT treatment in the United States.

According to a systematic review, people with HIT treated with lepirudin showed a relative risk reduction of clinical outcome (death, amputation, etc.) to be 0.52 and 0.42 when compared to patient controls. In addition, people treated with argatroban for HIT showed a relative risk reduction of the above clinical outcomes to be 0.20 and 0.18. Lepirudin production stopped on May 31, 2012.

In 2004 the first adequately large scale study on the natural history and long-term prognosis of this condition was reported; this showed that at 16 months follow-up 57.1% of patients had full recovery, 29.5%/2.9%/2.2% had respectively minor/moderate/severe symptoms or impairments, and 8.3% had died. Severe impairment or death were more likely in those aged over 37 years, male, affected by coma, mental status disorder, intracerebral hemorrhage, thrombosis of the deep cerebral venous system, central nervous system infection and cancer. A subsequent systematic review of nineteen studies in 2006 showed that mortality is about 5.6% during hospitalisation and 9.4% in total, while of the survivors 88% make a total or near-total recovery. After several months, two thirds of the cases has resolution ("recanalisation") of the clot. The rate of recurrence was low (2.8%).

In children with CVST the risk of death is high. Poor outcome is more likely if a child with CVST develops seizures or has evidence of venous infarction on imaging.

Options include:

- Medications alone (an antiplatelet drug (or drugs) and control of risk factors for atherosclerosis).

- Medical management plus carotid endarterectomy or carotid stenting, which is preferred in patients at high surgical risk and in younger patients.

- Control of smoking, high blood pressure, and high levels of lipids in the blood.

The goal of treatment is to reduce the risk of stroke (cerebrovascular accident). Intervention (carotid endarterectomy or carotid stenting) can cause stroke; however, where the risk of stroke from medical management alone is high, intervention may be beneficial. In selected trial participants with asymptomatic severe carotid artery stenosis, carotid endarterectomy reduces the risk of stroke in the next 5 years by 50%, though this represents a reduction in absolute incidence of all strokes or perioperative death of approximately 6%. In most centres, carotid endarterectomy is associated with a 30-day stroke or mortality rate of < 3%; some areas have higher rates.

Clinical guidelines (such as those of National Institute for Clinical Excellence (NICE) ) recommend that all patients with carotid stenosis be given medication, usually blood pressure lowering medications, anti-clotting medications, anti-platelet medications (such as aspirin or clopidogrel), and especially statins (which were originally prescribed for their cholesterol-lowering effects but were also found to reduce inflammation and stabilize plaque).

NICE and other guidelines also recommend that patients with "symptomatic" carotid stenosis be given carotid endarterectomy urgently, since the greatest risk of stroke is within days. Carotid endarterectomy reduces the risk of stroke or death from carotid emboli by about half.

For people with stenosis but no symptoms, the interventional recommendations are less clear. Such patients have a historical risk of stroke of about 1-2% per year. Carotid endarterectomy has a surgical risk of stroke or death of about 2-4% in most institutions. In the large Asymptomatic Carotid Surgery Trial (ACST) endarterectomy reduced major stroke and death by about half, even after surgical death and stroke was taken into account. According to the Cochrane Collaboration the absolute benefit of surgery is small. For intervention using stents, there is insufficient evidence to support stenting rather than open surgery, and several trials, including the ACST-2, are comparing these 2 procedures.

If restenosis occurs without a stent, it is usually treated with more angioplasty. Once restenosis has occurred and been treated by angioplasty, the chances of restenosis occurring again are increased by a factor of 2. This treatment is also used if restenosis occurs at either the proximal or distal end of the stent.

If restenosis occurs within a stent (also known as in-stent stenosis), it may be treated with repeated angioplasty and insertion of another stent inside the original, sometimes with a drug-eluting stent.

Over the past 5 years, ISR is preferentially treated with a drug eluting balloon, which is a balloon coated with the same anticancer drugs that prevent restenosis. The Balloon avoids the need for a double layer of metal which is used when an in-stent restenosis is treated with another stent within the original stent

Alternative treatments include brachytherapy, or intracoronary radiation. The radiation kills cells and inhibits tissue growth (similar to a patient undergoing cancer therapy).

Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. The goal of the prophylactic treatment with warfarin is to maintain the patient's INR between 2.0 and 3.0. It is not usually done in patients who have had no thrombotic symptoms.

Anticoagulation appears to prevent miscarriage in pregnant women. In pregnancy, low molecular weight heparin and low-dose aspirin are used instead of warfarin because of warfarin's teratogenicity. Women with recurrent miscarriage are often advised to take aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle. In refractory cases plasmapheresis may be used.