Scientists discover rare genetic condition that attacks kids’ immune systems
Coagulopathies: Abnormal Blood-clotting And Bleeding Disorders
Haemostasis is the prevention of unwanted blood loss; this process is interrupted by blood-clotting and bleeding disorders
AbstractPlatelets and blood-clotting factors are critical for haemostasis, which is the prevention of unwanted blood loss, usually following injury or trauma. Coagulopathies can manifest as either abnormal clotting or abnormal bleeding. Pathologies that cause abnormal clotting include thromboses in arteries or emboli from deep vein thromboses; these can both restrict blood flow to vital organs. A hypercoagulable state, such as factor V Leiden, can increase the risk of developing such blood clots. Pathologies that can cause abnormal bleeding include haemophilia and von Willebrand disease. Finally, disseminated intravascular coagulation presents as both abnormal blood clotting and abnormal bleeding; it can be a life-threatening complication of many conditions, including sepsis.
Citation: Nigam Y, Knight J (2024) Coagulopathies: abnormal blood-clotting and bleeding disorders. Nursing Times [online]; 120: 10.
Authors: Yamni Nigam is professor, John Knight is associate professor; both at the School of Health and Social Care, Swansea University.
Haemostasis is the physiological arrest or halting of bleeding, a complex but balanced process that helps stop blood loss. Disruption of this balance can cause bleeding or thrombotic events, which may require clinical intervention (Favaloro et al, 2023).
On injury, when a blood vessel is damaged, it immediately constricts to reduce blood loss. The platelets (tiny cellular fragments that are present in blood) come together to form a plug. This plug is then reinforced by the activation of a cascade of clotting factors (Fig 1), culminating in the conversion of the plasma protein fibrinogen into a strong and tough protein, fibrin. This leads to blood coagulation and the creation of a more robust, permanent clot (Barmore et al, 2023).
This article – the third in a series about the pathophysiology of blood – explores coagulation disorders that affect the body's ability to clot blood, which then manifests as either abnormal clotting or abnormal bleeding.
Platelets and clotting factorsPlatelets (thrombocytes) are tiny, irregular, disc-shaped fragments of larger cells called megakaryocytes, which develop in the bone marrow. Platelets circulate in the blood and are also stored in the spleen. Critically important in the process of haemostasis, an individual's platelet count determines their ability to clot blood effectively when needed.
A normal platelet count ranges from 150,000-450,000 per microlitre (µl) of blood. A platelet count of >450,000/µl is a condition called thrombocytosis and may predispose people to abnormally form clots (Knight et al, 2024). A platelet count of <150,000/µl is known as thrombocytopenia and may lead to abnormal bleeding (Schlappi et al, 2018).
"The complex process of haemostasis results in the formation of a clot"
The platelet plugIn normal conditions, platelets do not stick together or to the walls of healthy blood vessels. However, when a blood vessel is damaged, its inner lining tears, exposing collagen fibres in the tissue beneath. These collagen fibres become covered with a protein called von Willebrand factor, which is released by cells lining the blood vessels. Von Willebrand factor attracts platelets, causing them to stick to the exposed collagen (Cortes et al, 2023). As the platelets stick, they release three key chemicals that help with clotting: serotonin, adenosine diphosphate (ADP) and thromboxane A2 (TxA2) (Knight et al, 2024).
Serotonin helps to stimulate continued vasoconstriction, while ADP and TxA2 attract more platelets to the injury site. This causes membrane changes that render arriving platelets stickier and flatter. These flattened platelets adhere to the platelets that are already stuck to the collagen. Platelets in this second layer now also degranulate, releasing the three main platelet-derived factors mentioned above, thereby attracting even more platelets (Periayah et al, 2017). The resulting positive feedback ensures that layer upon layer of platelets aggregate, leading to the rapid formation of the platelet plug (Fig 2). This plug can be quite fragile and may be washed away if blood flow in the injured vessel is too vigorous, so it needs to be stabilised by the fibrin clot (Barmore et al, 2023).
The fibrin clotTo reinforce the platelet plug and stop blood loss, a more robust clot needs to be formed. This relies on the synthesis of a tough, fibrous, rope-like protein called fibrin. Fibrin forms a meshwork around the platelet plug, sealing the injured vessel and trapping blood cells. Fibrin is formed from the plasma protein fibrinogen in a complex series of reactions involving several blood-clotting factors (I-XIII); this can proceed via the extrinsic or intrinsic pathway (Barmore et al, 2023) (Fig 1).
The extrinsic pathway is triggered by any external trauma that causes blood to exit from damaged vessels. Clotting factor VII interacts with tissue factor, which is a large protein found on the surface of many cells and on the cells lining the blood vessels when they are damaged. The complex of tissue factor plus activated factor VII triggers the clotting mechanisms in seconds, leading to the formation of activated factor X (Knight et al, 2024).
The intrinsic pathway refers to clotting factors that are intrinsic to blood. When blood vessel walls are damaged, collagen fibres are exposed. Contact with collagen fibres activates a protein known as Hageman factor (factor XII). Over several minutes, a sequence of reactions unfolds, wherein each factor activates the next (Barmore et al, 2023) (Fig 1).
The extrinsic and intrinsic pathways meet at a shared point called the common pathway, in which the last part of coagulation can be summarised in three major steps:
This complex process of haemostasis results in the formation of a clot, transforming blood from a free-flowing liquid into a gel-like, solid substance that prevents further bleeding and blood loss. Fibrin then acts as scaffolding, onto which new tissues grow during the healing process (Culvert, 2024).
After the injury is healed, the fibrin clot is dissolved and removed from the body through a process called fibrinolysis. This is essential because, if clots remained in place, they could dislodge, travel in the circulation and get stuck in important blood vessels, thereby impeding blood flow (Risman et al, 2023).
The fibrinolytic system is constantly in operation, removing unnecessary clots. The key enzyme in this cascade of reactions is plasmin. Tissue plasminogen activator (a protein released from cells lining the blood vessels) converts an inactive plasma protein called plasminogen (produced by the liver) into plasmin. Plasmin splits fibrin and fibrinogen into fragments known as fibrin-degradation products (D-dimers), thereby dissolving the clot. A D-dimer blood test is often used to determine whether a patient has recently formed any blood clots (Culvert, 2024).
To limit the formation of clots to the site of injury and prevent them from growing too large, the coagulation cascade is regulated by different anticoagulant mechanisms. Two proteins – protein C and protein S – form a complex that inactivates factors V and VIII. Additionally, a protein called antithrombin III directly decreases the production of thrombin and inactivates factor X (Padda et al, 2023).
Any condition that causes an imbalance between thrombogenic (clot-forming) and antithrombogenic (anticlot-forming) mechanisms predisposes an individual to an increased risk of either abnormal bleeding or abnormal blood-clot formation (Hernández Castillo, 2020). These coagulopathies are conditions that adversely affect the body's normal blood-clotting activities, and are discussed below.
Coagulopathies that can cause abnormal clotting ThrombosisAmong the most significant life-threatening pathologies, thrombosis is a major blood coagulopathy. Thrombosis is the formation of unwanted thrombi (clots) in blood vessels. If anticlotting mechanisms fail, or are overwhelmed, these thrombi – with constituent platelets, fibrin and accumulating blood cells (Fig 3) – can narrow or block a vessel. This can restrict blood supply to the tissues being fed by that particular vessel, which can have serious – even fatal – outcomes, such as strokes or heart attacks. Emboli (fragments of clots) may also break away and lodge in distant vessels, particularly the lungs or brain (Knight et al, 2024).
In arterial thrombosis, a thrombus blocks an artery carrying oxygen-rich blood to an organ. In venous thrombosis, it blocks a vein, causing deep vein thrombosis (DVT). Thrombi and emboli can occlude any part of the circulation, but the coronary and cerebral arteries, and the deep veins of the calf and pelvis are most often affected (Knight et al, 2024).
DVTs are clots that develop in the deep venous circulation of an upper or lower limb and can present as pain and swelling in the affected limb. Emboli can migrate to the lungs, causing a pulmonary embolism. The pathophysiology of DVT formation has not been fully explained, but the current thinking is that the disturbed flow of blood around venous valves makes them uniquely vulnerable to thrombus initiation and formation. This happens through endothelial activation, which allows the adhesion of platelets and leukocytes, contributing to the activation of blood coagulation and trapping blood cells (Navarrete et al, 2023).
There are risk factors that increase the probability of developing DVTs. DVTs are more likely to occur in people:
The risk of DVT is also five times higher during pregnancy and 60 times higher during the first three months after delivery than the risk for non-pregnant women (Pomp et al, 2008).
Studies have shown how leukocytes contribute to DVT. Within six hours of vessel flow being restricted, leukocytes overlay the endothelial surface. Of all leukocytes that are present in a thrombus, 70% are neutrophils; the remaining 30% are monocytes (Swystun and Liaw, 2016).
By releasing their internal nuclear content, neutrophils are capable of producing neutrophil extracellular traps (NETs). This remarkable defence is a network of extracellular strings of DNA that can bind pathogenic microbes. Platelets can stimulate neutrophils to form NETs, and red blood cells also bind to NETs with high affinity. This is thought to be a mechanism by which red blood cells are recruited into venous thrombi. As such, targeting NETs – through either degradation or release prevention – may provide a new way of treating thrombosis (Yao et al, 2023).
"It is believed that a hypercoagulable state occurs in patients with chronic obstructive pulmonary disease"
Hypercoagulable statesA hypercoagulable state (also known as thrombophilia) is a clinical disorder of the blood that increases the risk of developing thromboembolic disease and arterial blood clots. Hypercoagulable states are either primary (inherited) or secondary (acquired) conditions (Hernández Castillo, 2020).
There are many inherited hypercoagulable conditions. Factor V Leiden is the most common, and is more prevalent in people of European descent (Pastori et al, 2024). Under normal conditions, protein C regulates the coagulation cascade by inhibiting factor V. In factor V Leiden, there is a point mutation in the gene coding for factor V, which causes resistance to the anticoagulant effects of activated protein C. The factor V cannot be inactivated, which means it can continuously activate clotting factors downstream. This leads to unregulated production of thrombin and an increased risk of clot formation (Hernández Castillo, 2020).
Acquired hypercoagulable conditions are secondary states caused by conditions or situations that increase the risk of thrombosis, including:
Cancer can cause hypercoagulability due to an increased production of pro-coagulant factors, and due to malignant cells interacting with the inner lining of blood vessels. Smoking, inflammation, surgery and trauma can damage blood vessels, repeatedly triggering activation of the coagulation cascade. Inflammatory disorders can also activate the coagulation cascade, reduce natural anticoagulant mechanisms and impair blood-clot removal (Hernández Castillo, 2020).
It is also believed that a hypercoagulable state occurs in patients who have chronic obstructive pulmonary disease (COPD). It seems this can contribute to an increased incidence of thrombotic events (such as DVTs and venous thromboembolisms), thereby increasing the disease-related morbidity and mortality of COPD (Kyriakopoulos et al, 2021). This can be explained by hypoxia-induced erythropoiesis (red blood cell production) in response to decreased respiratory oxygen levels. Similarly, it has been found that there is a statistically significantly increased likelihood of thromboembolic events occurring at high altitude, where atmospheric oxygen availability is low (Li et al, 2022).
Erythropoiesis requires increased iron transport to the bone marrow, which occurs with the help of transferrin (a small plasma protein). As well as replenishing iron levels for increased red blood cell production, transferrin promotes blood coagulation by increasing thrombin and factor XII activities, and inhibiting antithrombin (Tang et al, 2020); therefore, an increased need for transferrin (and the transport of iron) may play a role in inducing blood coagulation and hypercoagulability.
Coagulopathies that can cause abnormal bleedingAbnormal bleeding disorders can manifest as a variety of clinical symptoms. These include:
Thrombocytopenia is a condition that can be inherited or acquired. It is characterised by a blood platelet count that is too low; this can occur if the bone marrow cannot make enough platelets or it destroys them (Smock and Perkins, 2014). Platelets are stored in the spleen for use when required but, when a person has thrombocytopenia, they remain pooled in the spleen and are not released into the blood. This is often due to an enlarged or overactive spleen, which can be caused by conditions such as liver disease, autoimmune disease or infection (Al-Salem, 2023). Other factors – such as lifestyle habits (for example, overconsumption of alcohol) and certain medicines – can also slow down the production of platelets (Smock and Perkins, 2014).
Heparin-induced thrombocytopenia can also be a serious complication for patients who are exposed to the blood anticoagulant heparin. The immune system causes platelets to clot in the presence of heparin, resulting in a drop in platelet levels (Nicolas et al, 2023).
HaemophiliaAs the various clotting factors all have vital roles to play in the formation of fibrin clots (Fig 1), a missing or deficient factor will seriously hamper an individual's ability to control blood loss. Haemophilia is the most common inherited clotting disorder. There are two major types, both of which are caused by a deficiency in a factor from the intrinsic pathway:
Symptoms of haemophilia include:
Haemophilia can be inherited or acquired.
Inherited haemophilia is caused by a mutation in a gene that provides instructions for making the clotting factor. This mutation can prevent the clotting protein from working properly or cause it to be missing altogether. The mutated gene is located on the X chromosome; therefore, inherited haemophilia is an "X-linked recessive hereditary disorder" that typically affects males, because they have only one X chromosome (Shoukat et al, 2020). As females have two X chromosomes, they are more likely to be carriers of the mutated gene than to develop inherited haemophilia themselves. However, manifestations of inherited haemophilia can sometimes be seen in carrier females. This is a result of an unfortunate skewed inactivation of the normal non-carrier X chromosome, causing the dominant manifestation of the disease. This can be severe enough to cause a life-threatening bleed (Shoukat et al, 2020).
Acquired haemophilia A (AHA) can occur when the body forms autoantibodies (antibodies that react with self-antigens) against blood-clotting factors – most commonly against factor VIII. In 15% of the healthy population, low titres of anti-factor VIII antibodies can be found anyway; these are often asymptomatic in presentation and not caused by an underlying disease (Mingot-Castellano et al, 2022). However, AHA has been associated with:
Patients with AHA may experience acute abnormal bleeding, without previous symptoms or family history. The bleeding pattern is usually subcutaneous bleeds (observed in 80% of patients), followed by muscular, gastrointestinal, genitourinary and retroperitoneal bleeds (Mingot-Castellano et al, 2022).
Haemophilia can be managed by intravenous administration of concentrates of the missing factor. However, non-factor products have recently been developed that facilitate the coagulation cascade (such as emicizumab) or block the anticoagulant pathway (such as concizumab).Clinical trials of these products are ongoing (Nogami and Shima, 2023).
"Haemophilia typically affects males, because they have only one X chromosome"
Von Willebrand diseaseVon Willebrand disease is an inherited bleeding disorder characterised by defects in the concentration, structure or function of von Willebrand factor, a vital molecule in the formation of the platelet plug (Du et al, 2023). Von Willebrand factor is also a carrier glycoprotein for factor VIII, and is synthesised in endothelial cells and megakaryocytes (Sabih and Babiker, 2023).
Low levels of von Willebrand factor are relatively common in the general population; however, not all patients experience clinically significant bleeding issues, so "a significant proportion of the patient population goes undiagnosed" (Sabih and Babiker, 2023). Indeed, a von Willebrand factor level of <30% indicates von Willebrand disease, so most cases are diagnosed only after investigating severe bleeding problems, such as:
Worldwide, it appears that more women than men are affected by von Willebrand disease (Leebeek and Eikenboom, 2016). In a systematic review of literature about the disease, Du et al (2023) found that bleeding was reported in 72-94% of patients, with mucocutaneous, gastrointestinal and oral bleeds being the most common. Life-threatening bleeding involving critical organs was also reported, although this was rare.
Von Willebrand factor replacement can be considered in patients with the most severe type of von Willebrand disease (type 3) (Sabih and Babiker, 2023).
Vitamin K deficiencyVitamins K1 and K2 are very important fat-soluble compounds. Sources of vitamin K1 are leafy greens and cruciferous vegetables; vitamin K2 is found in fermented foods, as well as being synthesised by microbes in the intestine. Many vitamin K dependent proteins are involved in essential processes, such as bone metabolism, cardiovascular health and blood clotting. With regards to this last function, vitamin K is essential for the synthesis of:
As such, vitamin K deficiency can contribute to abnormal bleeding, as well as poor bone development, osteoporosis and increased cardiovascular disease (Eden et al, 2023).
Vitamin K deficiency is present in 8-31% of healthy adults (Eden et al, 2023). However, bleeding or haemorrhage typically occurs in people with malabsorption syndromes (such as coeliac disease or inflammatory bowel disease, which can impede the absorption of vitamin K) or liver disease. Patients on medications such as warfarin (a blood thinner), which interferes with vitamin K metabolism, can also present with vitamin K deficiency and a reduced ability to clot blood if injured. Prolonged use of antibiotics can also disrupt the gut bacteria that synthesise vitamin K (Eden et al, 2023).
Vitamin K deficiency in newborn babies presents a distinct and critical concern for paediatric health care. As vitamin K cannot cross the placenta efficiently, every neonate is born with low-to-undetectable concentrations of it. Newborns with limited vitamin K reserves who do not receive timely intervention are susceptible to developing potentially life-threatening bleeding disorders. Prophylactic treatment for neonates involves administering an intramuscular injection of 0.5-1mg vitamin K1 within the first hour of birth (Ng and Loewy, 2018).
Disseminated intravascular coagulationDisseminated intravascular coagulation (DIC) is a rare but life-threatening condition. The pathological process is characterised by the widespread activation of the coagulation cascade, resulting in the formation of blood clots in the small blood vessels throughout the body. In a stark pathological contradiction, normal blood clotting is compromised and patients also present with considerable bleeding. This is because the body's clotting factors and platelets become consumed and depleted by the coagulation process, forming abnormal blood clots. The presence of both clotting and bleeding (Fig 5) results in a very serious and distressing condition, which can lead to compromised tissue blood flow and, ultimately, multiple organ damage (Iba et al, 2023).
DIC usually occurs as a complicating factor of another underlying condition, most commonly in patients who are critically ill. Causes include:
DIC is of critical concern for patients with sepsis: the mortality rate of sepsis-associated DIC is >30% (Iba et al, 2023). The prognosis for all patients with DIC depends on how much damage blood clots have caused to the body's tissues. Of those patients who survive, some will live with organ dysfunction or the results of amputation (Iba et al, 2023).
ConclusionThis article has explained the process of haemostasis, as well as exploring coagulopathies that cause abnormal blood-clot formation or abnormal bleeding.
References
Al-Salem AH (2023) Splenomegaly. In: The Spleen. Springer.
Barmore W et al (2023) Biochemistry, Clotting Factors. StatPearls Publishing.
Cortes GA et al (2023) Physiology, Von Willebrand Factor. StatPearls Publishing.
Costello RA et al (2024) Disseminated Intravascular Coagulation. StatPearls Publishing.
Culvert LL (2024) Fibrin degradation products test. Encyclopedia.Com, 11 September (accessed 12 September 2024).
Dammann K et al (2020) Operative hemostasis in trauma and acute care surgery: the role of biosurgical agents. In: Firstenberg MS, Stawicki SP (eds) Contemporary Applications of Biologic Hemostatic Agents Across Surgical Specialties. IntechOpen.
Du P et al (2023) Von Willebrand disease epidemiology, burden of illness and management: a systematic review. Journal of Blood Medicine; 14: 189-208.
Eden RE et al (2023) Vitamin K Deficiency. StatPearls Publishing.
Favaloro EJ et al (2023) Hemostasis and thrombosis: an overview focusing on associated laboratory testing to diagnose and help manage related disorders. Methods in Molecular Biology; 2663: 3-38.
Hernández Castillo A (2020) Hypercoagulable state: what is it, causes, pregnancy, diagnosis, treatment, and more. Osmosis.Org, 24 November (accessed 12 September 2024).
Iba T et al (2023) The pathophysiology, diagnosis, and management of sepsis-associated disseminated intravascular coagulation. Journal of Intensive Care; 11: 24.
Knight J et al (2024) Understanding Anatomy and Physiology in Nursing. Learning Matters.
Kyriakopoulos C et al (2021) Hypercoagulable state in COPD: a comprehensive literature review. Diagnostics (Basel); 11: 8, 1447.
Leebeek FWG, Eikenboom JCJ (2016) Von Willebrand's disease. The New England Journal of Medicine; 375: 2067-2080.
Li M et al (2022) Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude. Blood; 140: 19, 2063-2075.
Mehta P, Reddivari AKR (2023) Hemophilia. StatPearls Publishing.
Mingot-Castellano ME et al (2022) Acquired haemophilia A: a review of what we know. Journal of Blood Medicine; 13: 691-710.
National institute for Health and Care Excellence (2023) Deep vein thrombosis: what are the risk factors? Cks.Nice.Org.Uk, June (accessed 12 September 2024).
Navarrete S et al (2023) Pathophysiology of deep vein thrombosis. Clinical and Experimental Medicine; 23: 645-654.
Ng E, Loewy AD (2018) Guidelines for vitamin K prophylaxis in newborns. Paediatrics and Child Health; 23: 6, 394-397.
Nicolas D et al (2023) Heparin-induced Thrombocytopenia. StatPearls Publishing.
Nogami K, Shima M (2023) Current and future therapies for haemophilia: beyond factor replacement therapies. British Journal of Haematology; 200: 1, 23-34.
Osmosis (no date) Disseminated intravascular coagulation. Osmosis.Org (accessed12 September 2024).
Padda IS et al (2023) Protein C and S. StatPearls Publishing.
Pastori D et al (2024) Factor V Leiden thrombophilia. In: Adam MP et al (eds) GeneReviews. University of Washington.
Periayah MH et al (2017) Mechanism action of platelets and crucial blood coagulation pathways in hemostasis. International Journal of Hematology-Oncology and Stem Cell Research; 11: 4, 319-327.
Pomp ER et al (2008) Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. Journal of Thrombosis and Haemostasis; 6: 4, 632-637.
Risman RA et al (2023) Fibrinolysis: an illustrated review. Research and Practice in Thrombosis and Haemostasis; 7: 2, 100081.
Sabih A, Babiker HM (2023) Von Willebrand Disease. StatPearls Publishing.
Schlappi C et al (2018) Outcomes in mild to moderate isolated thrombocytopenia. Pediatrics; 142: 1, e20173804.
Shoukat HMH et al (2020) Skewed inactivation of X chromosome: a cause of hemophilia manifestation in carrier females. Cureus; 12: 10: e11216.
Smock KJ, Perkins SL (2014) Thrombocytopenia: an update. International Journal of Laboratory Hematology; 36: 3, 269-278.
Swystun LL, Liaw PC (2016) The role of leukocytes in thrombosis. Blood; 128: 6, 753-762.
Tang X et al (2020) Transferrin plays a central role in coagulation balance by interacting with clotting factors. Cell Research; 30: 119-132.
Tortora GJ, Derrickson BH (2011) Principles of Anatomy and Physiology. John Wiley & Sons.
Yao M et al (2023) Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy. Frontiers in Immunology; 14: 1198952.
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What Is Thrombotic Thrombocytopenic Purpura (TTP)?
Thrombotic thrombocytopenic purpura (TTP) is a rare, severe blood disorder that causes blood clots to form in small blood vessels.
TTP can affect children and adults. People may inherit the condition or develop it through certain health conditions or medical treatments.
The blood clots that form with TTP can restrict blood flow to the organs, leading to various health problems. Without prompt treatment, TTP can be life threatening.
This article looks at TTP symptoms, causes, diagnosis, treatment, and outlook.
TTP is a rare blood disorder that causes blood clots to form in the body's small blood vessels. These blood clots can restrict or block blood flow to the organs, causing damage and affecting organ function.
Platelets are blood cells that help the blood clot to prevent bleeding. The formation of blood clots with TTP uses up platelets, which means the blood does not have enough platelets to form the necessary clots. This can lead to bruising and bleeding under the skin.
Thrombotic refers to the formation of a blood clot in a blood vessel, and thrombocytopenic means a reduced platelet count. Purpura is the term for the bruises that occur due to bleeding under the skin.
TTP also destroys red blood cells faster than the body can produce them, causing hemolytic anemia.
TTP can be life threatening, and without treatment, it may lead to serious complications, including stroke or brain damage.
TTP occurs when people have a severe deficiency of the ADAMTS13 enzyme, a protein in the blood that controls blood clotting. Without enough ADAMTS13, excess blood clots form.
People may inherit TTP or acquire it during their lifetime. They can also inherit a faulty ADAMTS13 gene, which means the gene produces an ADAMTS13 enzyme that does not function properly.
In most diagnoses of inherited TTP, each parent has one copy of the faulty ADAMTS13 gene, but they do not have any TTP signs or symptoms. People with inherited TTP have two copies of the ADAMTS13 mutation, as they receive one copy of the genetic mutation from each parent.
People with acquired TTP have a normal ADAMTS13 gene, but the body creates antibodies that prevent the ADAMTS13 enzyme from working correctly. This may happen due to certain health conditions or medical treatments.
Inherited TTP usually occurs in infants and children. Acquired TTP usually develops in adulthood but can also occur in children.
Risk factors for developing TTP include:
A 2016 study notes that Black people are at an increased risk of developing TTP and suggests that genetic factors may be contributors to their increased risk.
Certain medications and substances may cause TTP, including:
A doctor will assess any symptoms of TTP involves a doctor performing a physical examination, as well as requesting and evaluating personal and family histories.
Signs of TTP may appear differently in each person and can be similar to those in other conditions. If a doctor suspects TTP, they will typically order a range of tests, such as:
People with TTP need immediate treatment, as delayed treatment may increase the risk of life threatening complications. Doctors may begin treatment before the results of ADAMTS13 testing can confirm a diagnosis.
Therapeutic plasma exchange (TPE) is the first-line treatment for acquired TTP. TPE replaces plasma, the liquid component of blood, with healthy donor plasma.
The new plasma supplies the right amount of ADAMTS13 enzyme and removes antibodies that damage the enzyme. People will have TPE daily until it resolves the issues from TTP.
Alongside TPE, people will also typically receive immunosuppressive drugs, such as glucocorticoids or rituximab, to target the antibodies that attack the ADAMTS13 enzyme.
Doctors use plasma infusion to treat inherited TTP. This delivers donor plasma intravenously to replace the ADAMTS13 enzyme deficiency.
In 2023, the Food and Drug Administration (FDA) approved the drug Adzynma for adults and children with inherited TTP.
Adzynma is a genetically engineered version of the ADAMTS13 enzyme. It works to replace the enzyme or reduce the risk of TTP symptoms, and may be a safe and effective TTP treatment.
If standard TTP treatments are not effective, healthcare professionals may prescribe surgery to remove the spleen. The spleen is an abdominal organ that produces antibodies that block the effects of the ADAMTS13 enzyme.
TTP is a rare blood disorder that causes blood clots to develop in small blood vessels. It can damage organs and lead to them not working properly.
It is important that people contact a doctor immediately if they have any symptoms of TTP. The condition can be life threatening, but prompt treatment can help prevent severe or fatal complications.
Treatment may include plasma replacement therapies, medications, and in some cases, surgery to remove the spleen.
To Your Health: Blood Clots
Published October 9, 2024 at 11:26 AM CDT
Listen • 1:44
The American Society of Hematology states, "Blood clotting, or coagulation, is an important process that prevents excessive bleeding when a blood vessel is injured. Platelets and proteins in your plasma work together to stop the bleeding by forming a clot over the injury. Typically, your body will naturally dissolve the blood clot after the injury has healed. Sometimes, however, clots form on the inside of vessels without an obvious injury or do not dissolve naturally. These situations can be dangerous and require accurate diagnosis and appropriate treatment.
The most dangerous types of blood clots are Deep Vein Thrombosis and Pulmonary Embolism.
Deep Vein Thrombosis occurs when a blood clot forms in one of the deep veins of your body, usually in your legs, but sometimes in your arm. Clots can break off from this and travel to the lung, causing a pulmonary embolism, which can be fatal.
There are variety of risk factors for blood clots, including:Major surgery, such as a hip replacementMajor trauma, such as a car accidentSmokingUse of birth controlObesityPregnancy and ChildbirthSitting for long periods, especially during travel or confinement to bedand Thrombophilia, or clotting disorders, such as the inherited Factor V Leiden which is particularly dangerous for pregnant women.
The prevention and treatment of blood clots primarily involves the use of anticoagulant medications or, as they are commonly referred to, "blood thinners."
Resources:http://www.Hematology.Org/Patients/Clots/https://www.Stoptheclot.Org/about_natt-2/
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