Why Do I Have So Many Blood Clots? Causes Explained

Recurrent blood clots rarely have a single explanation. When someone develops clots repeatedly, it usually means one or more underlying factors are persistently tilting the body’s clotting system toward overactivity. These factors range from inherited gene mutations carried since birth to conditions acquired later in life, and in many cases, several of them stack on top of each other. Understanding which causes apply to you is the first step toward figuring out why your body keeps forming clots it shouldn’t.

How the Body Decides to Clot

Your blood is constantly balancing two opposing tasks: staying liquid enough to flow freely and being ready to solidify the instant a vessel is damaged. Three broad forces govern that balance, a concept physicians have recognized since the mid-1800s. The first is the composition of the blood itself, meaning the levels of clotting proteins, platelets, and natural anticoagulants circulating in your plasma. The second is the condition of the blood vessel walls, which release signals that either promote or prevent clotting. The third is blood flow: when blood moves too slowly or pools in one spot, clots are more likely to form.¹

Anything that disturbs one or more of these three forces can push you toward clotting. Risk factors for recurrent clots work by decreasing blood flow, activating the vessel lining, ramping up immune responses, boosting platelet activity, or changing the concentrations of pro- and anticoagulant proteins in the blood.² In people who keep getting clots, more than one of these mechanisms is often at work simultaneously.

Inherited Clotting Disorders

Some people are born with gene mutations that make their blood clot more easily than normal. These inherited thrombophilias are among the most common reasons for unexplained recurrent clots, especially in younger adults who develop them without obvious triggers like surgery or immobilization.

The most prevalent inherited risk factor among people of European descent is a mutation called Factor V Leiden, which makes one of the body’s key clotting proteins resistant to being switched off by a natural anticoagulant. Roughly 5% of the Caucasian population carries at least one copy of this mutation.³ A second common mutation, called the prothrombin G20210A variant, increases production of a clotting protein called prothrombin. Together, these two mutations are the most frequent inherited causes of abnormal clotting.⁴

Carrying just one of these mutations may not dramatically raise your risk of a second clot. One study found that carrying Factor V Leiden alone did not increase the chance of recurrent deep vein thrombosis compared with having neither mutation. But carrying both Factor V Leiden and the prothrombin mutation together roughly tripled the risk of spontaneous recurrence, and that risk climbed even higher when the first clot had also been unprovoked.⁵ The picture, however, is not perfectly settled. A separate large study found that even people who were homozygous for Factor V Leiden or carried both mutations did not show a statistically elevated recurrence risk after adjustments for age, sex, and other factors.⁶ This disagreement in the research means that a positive genetic test alone does not guarantee repeated clots, nor does a negative test rule out other causes.

Deficiencies in Natural Anticoagulants

Your body produces its own internal anticoagulants, proteins that keep clotting in check. The most important are antithrombin, protein C, and protein S. Inherited deficiencies in any of these proteins are rarer than Factor V Leiden but tend to carry a higher lifetime risk of clotting. A cooperative study across dozens of families found that the probability of developing at least one clot reached 80% to 90% by age 50 to 60 in people with any of these deficiencies.⁷

The relationship between these protein levels and clot risk is not a simple on-off switch. Research shows that as plasma levels of antithrombin, protein C, or protein S drop below normal, the risk of a clot rises in a continuous, accelerating fashion. For every modest decrease in antithrombin levels, clot risk jumped by about 40%, while equivalent drops in protein C or protein S each raised the risk by about 13%.⁸ In other words, even mildly low levels matter, and the lower they go, the worse the risk becomes.

Antiphospholipid Syndrome

Not all clotting disorders are inherited. Antiphospholipid syndrome is an autoimmune condition in which the body produces antibodies that attack its own clotting-regulation system. These antiphospholipid antibodies, particularly those targeting a protein called beta-2 glycoprotein I, drive clot formation through several routes at once: they interfere with natural anticoagulant reactions, disrupt the cells involved in clotting, and trigger the complement immune system.⁹ These antibodies are not merely markers of risk; they have been shown to actively cause a hypercoagulable state in both laboratory and animal studies.¹⁰

Antiphospholipid syndrome is one of the most important diagnoses to catch in someone with recurrent clots, because it often requires long-term (sometimes lifelong) anticoagulation. It can occur on its own or alongside other autoimmune diseases like lupus. It is also a major cause of recurrent pregnancy loss, making it especially relevant for women who develop clots during or around pregnancy.

Cancer and Clotting

An unexplained blood clot, particularly one that seems to come out of nowhere, can occasionally be the first sign of an undiagnosed cancer. This link between malignancy and clotting has been recognized for well over a century and is sometimes called Trousseau’s syndrome. Cancer cells themselves generate clotting factors, release inflammatory signals, and interact directly with blood vessel walls to create a procoagulant environment.¹¹ On top of that, cancer treatments like chemotherapy and surgery add their own clotting risks to the mix.¹²

This does not mean every recurrent clot signals cancer. But when someone over 40 develops an unprovoked clot and standard thrombophilia testing comes back negative, physicians will often screen for an occult malignancy, particularly cancers of the pancreas, lung, ovary, and brain, which are the types most strongly linked to abnormal clotting.

Chronic Inflammation and Autoimmune Disease

Inflammatory conditions can shift your clotting balance even without a specific genetic mutation. Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, is a clear example. The chronic inflammation in these conditions activates the clotting cascade, raising the risk of both deep vein thrombosis and pulmonary embolism.¹³ This risk is not limited to disease flares; emerging research points to gut microbiome disruption as an additional driver of clotting in these patients.¹⁴

Other inflammatory and autoimmune conditions, from rheumatoid arthritis to nephrotic syndrome, can similarly push the clotting system out of balance. The common thread is that persistent inflammation makes blood vessel walls stickier, boosts the production of clotting proteins, and impairs the body’s natural anticoagulant defenses. If you have a chronic inflammatory disease and keep developing clots, the inflammation itself may be a major contributor, separate from any genetic predisposition.

Hormones and Contraceptives

Estrogen is one of the most well-known environmental triggers for blood clots, which is why oral contraceptives, hormone replacement therapy, and pregnancy all increase clotting risk. Synthetic estrogen (ethinyl estradiol), the type used in most combined birth control pills, has a particularly strong effect on liver-produced clotting factors compared with natural estrogen.¹⁵ Newer formulations using estradiol or estradiol valerate were developed partly to reduce this metabolic impact.

Hormonal risk alone rarely causes repeated clots. But when combined with an inherited mutation like Factor V Leiden, the risk multiplies significantly. A young woman carrying Factor V Leiden who takes combined oral contraceptives, for instance, may face a clotting risk many times higher than someone with only one of those factors. This is one reason physicians sometimes recommend thrombophilia testing before prescribing estrogen-containing contraceptives to women with a personal or strong family history of clots.

Structural and Anatomical Causes

Sometimes the problem is not in the blood chemistry at all but in the physical layout of the blood vessels. May-Thurner syndrome occurs when the right common iliac artery compresses the left common iliac vein in the pelvis, creating a bottleneck that slows blood flow in the left leg. This makes the left leg disproportionately vulnerable to deep vein thrombosis.¹⁶ If you keep getting clots specifically in your left leg and other testing is unrevealing, your physician may investigate this possibility with imaging.

A related condition, Paget-Schroetter syndrome, affects the upper body. It happens when the subclavian vein gets compressed as it passes through a narrow space between the collarbone and first rib. Repetitive overhead arm movements, common in athletes like swimmers and baseball players, cause microtrauma to the vein in this compressed space, eventually triggering a clot in the arm or shoulder.¹⁷ These anatomical causes are worth knowing about because they are treatable, often with procedures that relieve the compression, and they can be missed if physicians focus exclusively on blood-based explanations.

When Medications Cause Clots

In a cruel irony, one of the medications used to prevent clots can sometimes cause them. Heparin-induced thrombocytopenia, or HIT, is a condition in which the immune system reacts to heparin (a common anticoagulant given in hospitals) by producing antibodies that activate platelets. The result is a paradoxical combination: the platelet count drops, yet the risk of dangerous clots goes up.¹⁸ A similar mechanism was seen in rare cases of vaccine-induced immune thrombotic thrombocytopenia during the COVID-19 pandemic, where platelet-activating antibodies formed without any heparin exposure at all.

HIT typically develops 5 to 10 days after starting heparin and is more common with unfractionated heparin than with the low-molecular-weight versions. It is diagnosed through a combination of clinical scoring and laboratory testing for the offending antibodies.¹⁹ Recognizing HIT quickly matters enormously, because the treatment is to stop heparin immediately and switch to a different type of anticoagulant.

Travel, Immobility, and Lifestyle Factors

You do not need an underlying disorder for blood to clot in the wrong place. Prolonged immobility is one of the most common real-world triggers. Long-haul flights combine several risk factors at once: sitting still for hours slows blood flow in the legs, cabin air pressure changes reduce oxygen levels, and low humidity promotes dehydration, all of which nudge the body toward a more clot-prone state.²⁰ The same logic applies to long car rides, bed rest after surgery, or being hospitalized for any reason. For someone who already carries a genetic or acquired risk factor, these situational triggers can be the final push that produces a clot.

Obesity adds to the picture by increasing the baseline level of inflammation in the body and raising intra-abdominal pressure, which compresses pelvic veins in much the same way as May-Thurner syndrome. Smoking damages blood vessel walls, and chronic dehydration reduces blood volume, making it more viscous. None of these lifestyle factors alone tends to cause repeated clots in otherwise healthy people, but they can turn a mild inherited tendency into a clinical problem.

Post-Infection Clotting and COVID-19

The COVID-19 pandemic brought the link between infection and clotting into sharp public awareness. SARS-CoV-2 proved unusually effective at promoting clots, and emerging evidence describes a process in which the virus triggers inflammation of blood vessel walls, overactivation of platelets, and formation of unusual fibrin-based microclots that are resistant to the body’s normal clot-dissolving mechanisms.²¹ These abnormalities of blood vessels and coagulation can persist well beyond the acute infection and affect multiple organ systems, which is one proposed explanation for some long COVID symptoms.

COVID-19 is not unique in this respect, though it is the most dramatic recent example. Other severe infections, particularly those that cause systemic inflammation or sepsis, can transiently push the clotting system into overdrive. A rare blood condition called paroxysmal nocturnal hemoglobinuria, which involves ongoing destruction of red blood cells, also creates a persistently clot-prone state through complement activation, endothelial damage, and platelet activation.²²

Arterial Versus Venous Clots

Not all blood clots are the same, and the type you develop can hint at the underlying cause. Venous clots, which form in the deep veins of the legs or pelvis, are made up mostly of red blood cells and fibrin fibers, giving them a dark, jelly-like appearance. Arterial clots, which form in arteries and cause heart attacks and strokes, have a very different structure: they are dominated by fibrin and platelets, with far fewer red blood cells.²³

This distinction matters because the risk factors diverge. Venous clots are more closely tied to immobility, inherited thrombophilias, cancer, and hormonal factors. Arterial clots are driven more by atherosclerosis, high blood pressure, diabetes, and smoking. If you are developing clots in both systems, that is a red flag for a condition like antiphospholipid syndrome, which is one of the few disorders that raises the risk of both arterial and venous events.

What Happens After Repeated Clots

Recurrent venous clots are not just a series of acute events; they carry long-term consequences. Post-thrombotic syndrome develops when clot damage to the vein valves leads to chronic pooling of blood in the affected limb, causing swelling, pain, skin changes, and in severe cases, ulcers that are difficult to heal. Chronic thromboembolic pulmonary hypertension can develop after repeated pulmonary emboli scar the lung arteries, raising the blood pressure in the lungs permanently.²⁴ Impaired resolution of the original clot is the common thread behind both complications.

These chronic complications are a major reason physicians take recurrent clots seriously even after each individual episode is treated. Preventing the next clot matters not just because the clot itself is dangerous but because each additional event raises the odds of lasting vascular damage.

How Long Anticoagulation Should Last

After an initial course of blood thinners, typically three to six months, the key question becomes whether to stop or continue indefinitely. About half of people with an unprovoked first deep vein thrombosis or pulmonary embolism will have a recurrence within ten years of stopping anticoagulation.²⁵ That statistic alone makes a strong case for long-term treatment, but the trade-off is real: every day on blood thinners carries a risk of major bleeding. The decision involves weighing the severity and frequency of past clots, the presence of identifiable risk factors, and the patient’s bleeding risk and personal preferences.²⁶

For someone with a clear provoked clot, say one triggered by surgery and bed rest, the risk of recurrence after stopping treatment is low, and short-term anticoagulation usually suffices. For someone with an unprovoked clot, an identified inherited thrombophilia, or antiphospholipid syndrome, the conversation about indefinite anticoagulation becomes much more pressing. There is no universal formula; it is a decision that needs revisiting over time as new risk factors emerge or existing ones change.

Why Factor V Leiden Is So Common

It seems counterintuitive that a mutation causing dangerous clots could be carried by one in twenty people of European descent, but Factor V Leiden may have conferred survival advantages that kept it in the gene pool. Carriers have been reported to experience less acute blood loss, lighter menstrual periods, a lower risk of brain bleeds, milder hemophilia symptoms when they co-inherit a bleeding disorder, and better survival during severe sepsis. There is even evidence of higher fertility in both men and women who carry the mutation.²⁷

The mutation’s prevalence varies dramatically by geography. It peaks at over 12% in Cyprus and follows a pattern across Europe consistent with spread from an Anatolian origin during the Neolithic period, when farming populations migrated westward. It is virtually absent in Inuit populations and very rare among French Basques.²⁸ This geographic pattern helps explain why recurrent clotting from inherited thrombophilia is more common in some ethnic groups than others, and why thrombophilia testing panels were largely designed around mutations prevalent in populations of European ancestry. If your background is East Asian, African, or Indigenous American, the standard panel may miss risk factors more relevant to you.