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 best course of treatment varies from case to case. The physician must take into account the details in the case before deciding on the appropriate treatment. No treatment is effective for every patient.

Treatment depends on many factors, including:

- Location of lesions

- Anatomy of lesions

- Patient risk factors

- Procedural risk

- Clinical presentation of symptoms

- Duration of symptoms

- etc.

Early treatment is essential to keep the affected limb viable. The treatment options include injection of an anticoagulant, thrombolysis, embolectomy, surgical revascularisation, or amputation. Anticoagulant therapy is initiated to prevent further enlargement of the thrombus. Continuous IV unfractionated heparin has been the traditional agent of choice.

If the condition of the ischemic limb is stabilized with anticoagulation, recently formed emboli may be treated with catheter-directed thrombolysis using intraarterial infusion of a thrombolytic agent (e.g., recombinant tissue plasminogen activator (tPA), streptokinase, or urokinase). A percutaneous catheter inserted into the femoral artery and threaded to the site of the clot is used to infuse the drug. Unlike anticoagulants, thrombolytic agents work directly to resolve the clot over a period of 24 to 48 hours.

Direct arteriotomy may be necessary to remove the clot. Surgical revascularization may be used in the setting of trauma (e.g., laceration of the artery). Amputation is reserved for cases where limb salvage is not possible. If the patient continues to have a risk of further embolization from some persistent source, such as chronic atrial fibrillation, treatment includes long-term oral anticoagulation to prevent further acute arterial ischemic episodes.

Decrease in body temperature reduces the aerobic metabolic rate of the affected cells, reducing the immediate effects of hypoxia. Reduction of body temperature also reduces the inflammation response and reperfusion injury. For frostbite injuries, limiting thawing and warming of tissues until warmer temperatures can be sustained may reduce reperfusion injury.

The Infarct Combat Project (ICP) is an international nonprofit organization founded in 1998 to fight ischemic heart diseases through education and research.

With treatment, approximately 80% of patients are alive (approx. 95% after surgery) and approximately 70% of infarcted limbs remain vital after 6 months.

In those who have developed critically poor blood flow to the legs, it is unclear if autotransplantation of autologous mononuclear cells is useful or not.

Only one randomized controlled trial has been conducted comparing vascular bypass to angioplasty for the treatment of severe PAD. The trial found no difference in amputation-free survival between vascular bypass and angioplasty at the planned clinical endpoint, however the trial has been criticized as being underpowered, limiting endovascular options, and comparing inappropriate endpoints. As of 2017, two randomized clinical trials are being conducted to better understand the optimal revascularization technique for severe PAD and critical limb ischemia (CLI), the BEST-CLI (Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia) Trial, and the BASIL-2 (Bypass Versus Angio plasty in Severe Ischaemia of the Leg – 2 )Trial.

In 2011, pCMV-vegf165 was registered in Russia as the first-in-class gene therapy drug for treatment of peripheral artery disease, including the advanced stage of critical limb ischemia.

Oxygen consumption of skeletal muscle is approximately 50 times larger while contracting than in the resting state. Thus, resting the affected limb should delay onset of infarction substantially after arterial occlusion.

Low molecular weight heparin is used to reduce or at least prevent enlargement of a thrombus, and is also indicated before any surgery. In the legs, below the inguinal ligament, percutaneous aspiration thrombectomy is a rapid and effective way of removing thromboembolic occlusions. Balloon thrombectomy using a Fogarty catheter may also be used. In the arms, balloon thrombectomy is an effective treatment for thromboemboli as well. However, local thrombi from atherosclerotic plaque are harder to treat than embolized ones. If results are not satisfying, another angiography should be performed.

Thrombolysis using analogs of tissue plasminogen activator (tPA) may be used as an alternative or complement to surgery. Where there is extensive vascular damage, bypass surgery of the vessels may be necessary to establish other ways to supply the affected parts.

Swelling of the limb may cause inhibited flow by increased pressure, and in the legs (but very rarely in the arms), this may indicate a fasciotomy, opening up all four leg compartments.

Because of the high recurrence rates of thromboembolism, it is necessary to administer anticoagulant therapy as well. Aspirin and low molecular weight heparin should be administered, and possibly warfarin as well. Follow-up includes checking peripheral pulses and the arm-leg blood pressure gradient.

Non-occlusive disease has a poor prognosis with survival rate between 40-50%.

Cilostazol or pentoxifylline can improve symptoms in some. Cilostazol may improve walking distance for people who experience claudication due to peripheral artery disease, but there is no strong evidence to suggest that it improves the quality of life, decreases mortality, or decreases the risk of cardiovascular events.

Treatment with other drugs or vitamins are unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B-12 on hyperhomocysteinemia, a putative vascular risk factor, are near completion".

The treatment of mesenteric ischemia depends on the cause, and can be medical or surgical. However, if bowel has become necrotic, the only treatment is surgical removal of the dead segments of bowel.

In non-occlusive mesenteric ischemia, where there is no blockage of the arteries supplying the bowel, the treatment is medical rather than surgical. People are admitted to the hospital for resuscitation with intravenous fluids, careful monitoring of laboratory tests, and optimization of their cardiovascular function. NG tube decompression and heparin anticoagulation may also be used to limit stress on the bowel and optimize perfusion, respectively.

Surgical revascularisation remains the treatment of choice for mesenteric ischaemia related to an occlusion of the vessels supplying the bowel, but thrombolytic medical treatment and vascular interventional radiological techniques have a growing role.

If the ischemia has progressed to the point that the affected intestinal segments are gangrenous, a bowel resection of those segments is called for. Often, obviously dead segments are removed at the first operation, and a second-look operation is planned to assess segments that are borderline that may be savable after revascularization.

Non-Occlusive Disease (NOD) or Non-Occlusive Mesenteric Ischaemia (NOMI) is a life-threatening condition including all types of mesenteric ischemia without mesenteric obstruction. It affects mainly elderly patients above 50 years of age who suffer from cardiovascular disease (myocardial infarction, congestive heart failure or aortic insufficiency), hepatic, renal insufficiency or diabetes. It can be triggered also by a previous cardiac surgery with a consequent heart shock. It represents around 20% of cases of acute mesenteric ischaemia.

70% of patients with carotid arterial dissection are between the ages of 35 and 50, with a mean age of 47 years.

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.

The goal of treatment is to prevent the development or continuation of neurologic deficits. Treatments include observation, anticoagulation, stent implantation and carotid artery ligation.

The prognosis depends on prompt diagnosis (less than 12–24 hours and before gangrene) and the underlying cause:

- venous thrombosis: 32% mortality

- arterial embolism: 54% mortality

- arterial thrombosis: 77% mortality

- non-occlusive ischemia: 73% mortality.

In the case of prompt diagnosis and therapy, acute mesenteric ischemia can be reversible.

Available hind limb IR animal model are either artery vein ligation or tourniquet application (by rubber band or O-ring).

Possible treatments are the application of IR related-pathway derived drug/inhibitor and cell therapy. The study has been done a role for p53 in activating necrosis. During oxidative stress, p53 accumulates in the mitochondrial matrix and triggers mitochondrial permeability transition pore (PTP) opening. To the end of this, necrosis occurs by physical interaction with the PTP regulator cyclophilin D (CypD). The mitochondrial p53-CypD axis as an important contributor to oxidative stress-induced necrosis and implicates in disease pathology and possible treatment. Cyclosporine A, known as a potent the mitochondrial permeability transition pore (mPTP) opening inhibitor and extremely powerful in protecting cardiomyocytes from IR, normalized ROS production, decreased inflammation, and restored mitochondrial coupling during aortic cross-clamping in Rat hind limb IR model.

The treatment for thrombosis depends on whether it is in a vein or an artery, the impact on the person, and the risk of complications from 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.

Major risk factors for cerebral infarction are generally the same as for atherosclerosis: high blood pressure, Diabetes mellitus, tobacco smoking, obesity, and dyslipidemia. The American Heart Association/American Stroke Association (AHA/ASA) recommends controlling these risk factors in order to prevent stroke. The AHA/ASA guidelines also provide information on how to prevent stroke if someone has more specific concerns, such as Sickle-cell disease or pregnancy. It is also possible to calculate the risk of stroke in the next decade based on information gathered through the Framingham Heart Study.

Pneumatic, surgical tourniquets are frequently applied in the controlled environment of the operating room in order to control blood loss during an upper or lower extremity operative case. Aside from lower blood loss in itself, this improves visualization and surgical efficiency. Modern examples are found in many different sizes to accommodate different patients and sites of applications, with adult cuffs approximately 4" wide. This distributes the pressure over, generally, a broader area than field (emergency, combat) tourniquets. The cuff is typically attached to an adjustable pneumatic pump with a built-in timer. Surgical tourniquet times in excess of 2 hours have been associated with an increased risk of nerve damage (e.g., neuropraxia), likely related to both direct nerve compression as well as decreased arterial inflow and oxygenation. The ischemia-reperfusion injury associated with surgical tourniquets is typically not clinically apparent when used for less than 2 hours.

Emergency field tourniquets have been used for many centuries, and have seen a resurgence in the recent combat operations in Afghanistan and Iraq, as well as expanded use in civilian trauma and mass casualty settings. Expedient and widespread tourniquet use in the modern combat setting is frequently cited as a primary driver for increased survival following major battlefield trauma. These tourniquets are often 1-2" in width, which concentrates the pressure to a narrow band of tissue. They can result in tissue necrosis if kept in place for long periods, and should only be applied after other methods to control bleeding (e.g., elevation or direct pressure to the wound) have failed, except in settings where time does not allow waiting. Generally, tissue distal to a field tourniquet that has been in place for greater than 6 hours is considered likely to be non-viable.

In the same way that external compression tourniquets reduce or eliminate arterial blood flow, aortic cross clamping has the same effect. The Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) device achieves this as well. By design, these devices induce ischemia to the lower extremities (as a secondary effect, or less commonly as their primary use). Releasing the cross clamp or removing the REBOA initiates reperfusion, and IR injury to the lower extremities may follow.

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.

In mostly European experience with 69 patients during 1996-2016, the 5- and 10-year survival rates for SCLS patients were 78% and 69%, respectively, but the survivors received significantly more frequent preventive treatment with IVIG than did non-survivors. Five- and 10-year survival rates in patients treated with IVIG were 91% and 77%, respectively, compared to 47% and 37% in patients not treated with IVIG. Moreover, better identification and management of this condition appears to be resulting in lower mortality and improving survival and quality-of-life results as of late.

The second stage features the reabsorption of the initially extravasated fluid and albumin from the tissues, and it usually lasts 1 to 2 days. Intravascular fluid overload leads to polyuria and can cause flash pulmonary edema and cardiac arrest, with possibly fatal consequences. Death from SCLS typically occurs during this recruitment phase because of pulmonary edema arising from excessive intravenous fluid administration during the earlier leak phase. The severity of the problem depends on to the quantity of fluid supplied in the initial phase, the damage that may have been sustained by the kidneys, and the promptness with which diuretics are administered to help the patient discharge the accumulated fluids quickly. A recent study of 59 acute episodes occurring in 37 hospitalized SCLS patients concluded that high-volume fluid therapy was independently associated with poorer clinical outcomes, and that the main complications of SCLS episodes were recovery-phase pulmonary edema (24%), cardiac arrhythmia (24%), compartment syndrome (20%), and acquired infections (19%).

The prevention of episodes of SCLS has involved two approaches. The first has long been identified with the Mayo Clinic, and it recommended treatment with beta agonists such as terbutaline, phosphodiesterase-inhibitor theophylline, and leukotriene-receptor antagonists montelukast sodium.

The rationale for use of these drugs was their ability to increase intracellular cyclic AMP (adenosine monophosphate) levels, which might counteract inflammatory signaling pathways that induce endothelial permeability. It was the standard of care until the early 2000s, but was sidelined afterwards because patients frequently experienced renewed episodes of SCLS, and because these drugs were poorly tolerated due to their unpleasant side effects.

The second, more recent approach pioneered in France during the last decade (early 2000s) involves monthly intravenous infusions of immunoglobulins (IVIG), with an initial dose of 2 gr/kg/month of body weight, which has proven very successful as per abundant case-report evidence from around the world.

IVIG has long been used for the treatment of autoimmune and MGUS-associated syndromes, because of its potential immunomodulatory and anticytokine properties. The precise mechanism of action of IVIG in patients with SCLS is unknown, but it is likely that it neutralizes their proinflammatory cytokines that provoke endothelial dysfunction. A recent review of clinical experience with 69 mostly European SCLS patients found that preventive treatment with IVIG was the strongest factor associated with their survival, such that an IVIG therapy should be the first-line preventive agent for SCLS patients. According to a recent NIH survey of patient experience, IVIG prophylaxis is associated with a dramatic reduction in the occurrence of SCLS episodes in most patients, with minimal side effects, such that it may be considered as frontline therapy for those with a clear-cut diagnosis of SCLS and a history of recurrent episodes.

In medicine, May-Thurner syndrome (MTS), also known as the iliac vein compression syndrome, is a rare condition in which compression of the common venous outflow tract of the left lower extremity may cause discomfort, swelling, pain or blood clots, called deep venous thrombosis (DVT), in the iliofemoral vein.

The specific problem is compression of the left common iliac vein by the overlying right common iliac artery. This leads to pooling or stasis of blood, predisposing the individual to the formation of blood clots. Uncommon variations of MTS have been described, such as the right common iliac vein getting compressed by the right common iliac artery.

In the 21st century the May-Thurner syndrome definition has been expanded to a broader disease profile known as nonthrombotic iliac vein lesions (NIVL) which can involve both the right and left iliac veins as well as multiple other named venous segments. This syndrome frequently manifests as pain when the limb is dependent (hanging down the edge of a bed/chair) and/or significant swelling of the whole limb.

Blue toe syndrome is a situation that may reflect atherothrombotic microembolism, causing transient focal ischaemia, occasionally with minor apparent tissue loss, but without diffuse forefoot ischemia. The development of blue or violaceous toes can also occur with trauma, cold-induced injury, disorders producing generalized cyanosis, decreased arterial flow, impaired venous outflow, and abnormal circulating blood.

The terms "blue toe syndrome", "grey toe syndrome" and "purple toe syndrome" are sometimes used interchangeably.

Studies may include echocardiography, thoracic and abdominal CT or MRI, peripheral arterial run off imaging studies, hypercoagulopathy labs, and interrogation of syndromes that lead to peripheral vascular pathology.