Introduction

Blood doesn't just flow. It also needs to stop flowing in exactly the right place at exactly the right time. That balance is called hemostasis, and when it fails, the result is a blood clotting disorder.

These disorders sit in two opposing camps. In bleeding disorders, clots form too slowly or fall apart too easily, so injuries don't seal properly. In thrombotic disorders, clots form when they shouldn't, blocking healthy vessels and threatening organs. Both come from disruption to the same network of platelets, clotting factors, and vessel walls, just tipped in opposite directions.

Platelet disorders affect primary hemostasis (the platelet plug). Coagulation disorders, the focus of this article, affect secondary hemostasis (the clotting factors that build the fibrin mesh). They share symptoms, but the lab tests and treatments differ.

Coagulation (Hemostasis)

Hemostasis stops bleeding in four coordinated steps:

1. Vasoconstriction. The injured vessel's smooth muscle contracts, narrowing blood flow.
2. Primary hemostasis (platelet plug). Platelets stick to exposed collagen and clump together, forming a sticky preliminary seal.
3. Secondary hemostasis (coagulation cascade). Clotting factors activate one another in a chain, ending with fibrin strands woven through the plug.
4. Fibrinolysis. Once healing is done, plasmin dissolves the clot.

Coagulation is the third step. When it malfunctions, the result is either too little clot (bleeding) or too much (thrombosis).

Coagulation Cascade

Most textbooks still teach the classic two-pathway cascade because it maps neatly onto common lab tests:

• Intrinsic pathway (factors XII, XI, IX, VIII): measured by aPTT.
• Extrinsic pathway (factor VII, triggered by tissue factor): measured by PT/INR.
• Common pathway (factors X, V, II/prothrombin, I/fibrinogen, XIII): the final shared steps that produce thrombin, then fibrin, then a stable cross-linked clot.

In real life, the body uses a cell-based model: tissue factor on damaged cells initiates a small thrombin burst, that burst amplifies on platelet surfaces, then propagation generates enough thrombin to lock the clot in place. The two-pathway model is still useful for interpreting PT and aPTT results, but the cell-based model is what's actually happening in vivo. Knowing both helps you make sense of why someone with a single factor deficiency bleeds differently from someone with a global problem.

Throughout the cascade, natural anticoagulants (protein C, protein S, and antithrombin) keep clotting localized. When any of these are deficient, thrombosis risk rises.

Types of Blood Clotting Disorders

We can sort blood clotting disorders by origin (inherited vs acquired) and by direction (bleeding vs thrombotic).

Inherited Bleeding Disorders

Hemophilia A

• Cause: Mutation in the F8 gene on the X chromosome, leading to factor VIII deficiency. X-linked recessive inheritance, so males are affected far more often than females [7].
• Symptoms: Easy bruising, prolonged bleeding after surgery or dental work, deep joint bleeds (knees, elbows, ankles), and muscle hematomas. Severity is graded by factor VIII level: severe (<1%), moderate (1–5%), mild (5–40%).
• Diagnosis: Prolonged aPTT with normal PT, low factor VIII activity, and F8 gene testing.
• Treatment (now and emerging):
  • Factor VIII replacement with standard or extended half-life recombinant concentrates.
  • Emicizumab (Hemlibra), a subcutaneous bispecific antibody that mimics factor VIII's function. It is strongly recommended for severe hemophilia A with or without inhibitors [6].
  • Anti-TFPI therapies: Non-factor subcutaneous treatments like marstacimab (Hympavzi) and concizumab (Alhemo) rebalance hemostasis by inhibiting the tissue factor pathway inhibitor (TFPI). Marstacimab was FDA-approved in late 2024 for routine prophylaxis in hemophilia A or B without inhibitors, offering a novel steady-state approach [12].
  • Gene therapy: Valoctocogene roxaparvovec (Roctavian) was FDA-approved in 2023 for severe hemophilia A. While a scientific milestone, it has faced significant commercial challenges, resulting in BioMarin restricting its commercial focus and effectively withdrawing it from the European market in 2024 due to low uptake and reimbursement hurdles [5,13].

Hemophilia B

• Cause: Mutation in the F9 gene on the X chromosome, causing factor IX deficiency. Same inheritance pattern as hemophilia A.
• Symptoms: Clinically indistinguishable from hemophilia A; severity again tracks with factor activity.
• Diagnosis: Prolonged aPTT, normal PT, low factor IX activity.
• Treatment (now and emerging):
  • Factor IX replacement, including extended half-life products.
  • Anti-TFPI therapies: Subcutaneous marstacimab is also approved for hemophilia B without inhibitors, shifting the paradigm from exclusively intravenous factor replacement to steady-state subcutaneous prophylaxis [12].
  • Gene therapy: Etranacogene dezaparvovec (Hemgenix) and fidanacogene elaparvovec (Beqvez) are one-time AAV-mediated gene therapies. Both remain commercially available and represent transformative options for appropriate adults with moderate to severe disease [4,14].

von Willebrand Disease (vWD)

• Cause: Mutations in the VWF gene. Von Willebrand factor has two jobs: helping platelets stick to injured vessels and carrying factor VIII in the blood. So vWD causes a mixed primary–secondary hemostasis defect.
• Symptoms: Mucocutaneous bleeding dominates like nosebleeds, gum bleeding, easy bruising, and heavy menstrual periods (menorrhagia). Joint bleeds are uncommon except in severe type 3 disease.
• Diagnosis: Per the 2021 ASH/ISTH/NHF/WFH guidelines [3], the work-up combines a validated bleeding assessment tool with VWF antigen, VWF activity (using newer GPIb-binding assays where available), and factor VIII activity. A 2025 monitoring report has reaffirmed these recommendations.
• Treatment: Depends on type and severity [2]:
  • Desmopressin (DDAVP) for type 1 (suitable patients): releases stored vWF and factor VIII.
  • VWF concentrates (plasma-derived or recombinant vonicog alfa) for severe disease or when DDAVP isn't enough.
  • Tranexamic acid as an adjunct for mucosal bleeding.
  • Hormonal management for heavy menstrual bleeding.

Inherited Thrombophilias (Tendency to Clot)

These don't cause bleeding; they cause clots. Often silent until a major trigger (surgery, pregnancy, long-haul travel, oral contraceptives) reveals them.

• Factor V Leiden: A point mutation that makes factor V resistant to activated protein C, the body's brake. Most common inherited thrombophilia. Heterozygotes have a modestly raised DVT/PE risk; homozygotes more so.
• Prothrombin G20210A: A gene variant that increases prothrombin levels, raising clot risk.
• Protein C, protein S, and antithrombin deficiencies: Rarer but stronger risk factors. Antithrombin deficiency is the most thrombogenic of the three.
• Management: Often nothing in asymptomatic carriers. After a clot, anticoagulation with a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) or warfarin. Indefinite anticoagulation is considered after unprovoked or recurrent events.

Acquired Blood Clotting Disorders

Vitamin K Deficiency

• Cause: Vitamin K is needed to make factors II, VII, IX, X, and proteins C and S. Causes include poor diet, fat malabsorption, prolonged antibiotic use, and newborn low stores.
• Symptoms: Easy bruising, mucosal bleeding, gastrointestinal bleeding.
• Diagnosis: Prolonged PT (and later aPTT), corrected by vitamin K administration.
• Treatment: Oral or intravenous vitamin K. For active bleeding, four-factor prothrombin complex concentrate (4F-PCC) gives faster correction than fresh frozen plasma.

Hemorrhagic Disease of the Newborn (HDN)

• Cause: Newborns are born with low vitamin K stores and gut bacteria haven't yet colonized to produce more.
• Symptoms: Bleeding from the umbilical cord, gastrointestinal tract, or (most dangerously) intracranial hemorrhage.
• Diagnosis: Prolonged PT with risk factors and clinical picture.
• Treatment: Prophylactic intramuscular vitamin K at birth is standard of care and prevents most cases. This is one of the most successful prevention programs in pediatrics.

Liver Disease

• Cause: The liver makes almost all clotting factors except factor VIII and vWF. Severe liver disease impairs production.
• Symptoms: Easy bruising, mucosal bleeding, varices, alongside jaundice and ascites.
• Diagnosis: Prolonged PT and aPTT, low fibrinogen in advanced disease, often with thrombocytopenia.
• Treatment: Treat the underlying disease. For active bleeding or procedural prophylaxis, fresh frozen plasma, cryoprecipitate, or prothrombin complex concentrate can be used. Routine "correction" of an abnormal INR in a non-bleeding cirrhotic patient is no longer recommended. Viscoelastic testing (such as TEG or ROTEM) is now the standard of care for guiding transfusions in liver disease, as standard PT/INR fails to measure the parallel drop in natural anticoagulants, meaning a patient with an elevated INR may actually be hypercoagulable [16].

Disseminated Intravascular Coagulation (DIC)

DIC is a medical emergency in which the coagulation system fires everywhere at once. The 2025 ISTH update redefined DIC as "an acquired, life-threatening intravascular disorder characterized by systemic coagulation activation, dysregulated fibrinolysis, and endothelial injury, resulting in microthrombosis" [1].

• Causes: Sepsis, major trauma, obstetric emergencies (placental abruption, amniotic fluid embolism), certain cancers (especially acute promyelocytic leukemia), severe burns, snake envenomation.
• Pathophysiology: Widespread microthrombi consume platelets and clotting factors, so the patient simultaneously clots in small vessels and bleeds from large ones.
• Diagnosis: The 2025 ISTH framework introduces a phase-based approach — pre-DIC, early-phase DIC, and overt DIC. This update was specifically driven by the need to identify coagulopathy in sepsis and trauma patients early, allowing for targeted intervention before widespread consumptive coagulopathy makes bleeding irreversible [1].
• Treatment: Treat the underlying cause (antibiotics for sepsis, delivery for obstetric DIC, ATRA for APL). Supportive blood-product replacement uses platelets, fresh frozen plasma, and cryoprecipitate. Anticoagulation is selective and reserved for clearly thrombotic presentations.

Antiphospholipid Syndrome (APS)

• Cause: Autoantibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) against phospholipid-binding proteins. May be primary or associated with systemic lupus erythematosus [9].
• Symptoms: Arterial and venous thrombosis (DVT, PE, stroke at young ages), recurrent miscarriage, late pregnancy loss, livedo reticularis, thrombocytopenia.
• Diagnosis: Persistent antiphospholipid antibodies on two occasions ≥12 weeks apart, plus a qualifying clinical event.
• Treatment: Long-term anticoagulation [10]. Warfarin remains the preferred agent in triple-positive APS; DOACs are generally avoided in this subgroup because of higher recurrence rates. Pregnancy is managed with low-dose aspirin plus prophylactic low-molecular-weight heparin.

Heparin-Induced Thrombocytopenia (HIT)

HIT is not an antibody against a clotting factor. It is an IgG antibody against the platelet factor 4–heparin complex that paradoxically activates platelets and causes thrombosis, not bleeding, despite a falling platelet count [11].

• Symptoms: New thrombosis (often venous) 5–10 days after starting heparin, with a 30–50% drop in platelet count.
• Diagnosis: 4Ts score, then immunoassay (PF4-heparin ELISA), then functional confirmation (serotonin release assay).
• Treatment: Stop all heparin. Start a non-heparin anticoagulant (argatroban, bivalirudin, fondaparinux, or a DOAC in stable patients).

Other Acquired Causes

• Warfarin over-anticoagulation — reverse with vitamin K, 4F-PCC, or fresh frozen plasma depending on severity.
• Severe burns — combined endothelial injury, factor consumption, and dilution.
• Cancer-associated thrombosis (CAT) — Trousseau syndrome and general malignancy carry a high VTE risk. Direct oral anticoagulants (DOACs like apixaban, edoxaban, and rivaroxaban) have largely replaced low-molecular-weight heparin (LMWH) as the standard of care for CAT, except in patients with unresected gastrointestinal or genitourinary malignancies where the bleeding risk on DOACs remains too high [17].
• Oral contraceptives and pregnancy — estrogen-driven hypercoagulable states; risk multiplies in carriers of factor V Leiden or with smoking.
• Massive transfusion — dilutional coagulopathy. Modern massive transfusion protocols use 1:1:1 ratios of red cells, plasma, and platelets, with tranexamic acid given early in trauma.

Diagnosis of a Blood Clotting Disorder

Diagnosing a blood clotting disorder is a tiered process: history first, then a basic lab screen, then targeted confirmatory tests.

Clinical History

A focused bleeding and thrombosis history covers:

• Bleeding pattern: Spontaneous vs trauma-related, mucocutaneous vs deep tissue, joint bleeds.
• Surgical and dental history: Heavy bleeding after tooth extraction or tonsillectomy is a classic clue.
• Menstrual and obstetric history: Heavy periods since menarche, postpartum hemorrhage, recurrent miscarriage.
• Family history: Bleeding or clotting in first-degree relatives.
• Medications: Warfarin, heparin, DOACs, antiplatelets, NSAIDs, hormonal contraception.
• Comorbidities: Liver disease, kidney disease, malignancy, autoimmune disease.

Validated bleeding assessment tools (e.g., the ISTH-BAT) help quantify bleeding history and triage who needs further testing.

Physical Examination

Look for petechiae (pinpoint red spots, usually a platelet sign), ecchymoses (large bruises), mucosal bleeding, joint swelling, and signs of liver disease. In thrombosis, look for unilateral leg swelling, calf tenderness, and signs of pulmonary embolism such as tachypnea and hypoxia.

First-Line Laboratory Tests

• Prothrombin time (PT) / INR — extrinsic and common pathways.
• Activated partial thromboplastin time (aPTT) — intrinsic and common pathways.
• Platelet count — to separate primary from secondary hemostasis issues.
• Fibrinogen — low in DIC, advanced liver disease, hereditary fibrinogen disorders.
• D-dimer — raised in active thrombosis, DIC, recent surgery, pregnancy, infection.

A useful starting heuristic: isolated prolonged PT points toward factor VII or vitamin K issues; isolated prolonged aPTT points toward intrinsic-pathway problems (hemophilias, vWD, contact factor deficiencies); both prolonged suggest common pathway or global problems like liver disease and DIC.

Targeted Confirmatory Tests

• Specific factor assays (factor VIII, IX, XI, etc.) for hemophilias.
• VWF antigen, VWF activity, factor VIII activity for vWD.
• Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin IgG/IgM, anti-β2GPI IgG/IgM).
• Thrombophilia panel (factor V Leiden, prothrombin G20210A, protein C, protein S, antithrombin) — only when indicated; routine screening is discouraged.
• Liver function tests, vitamin K assessment, and autoimmune work-up as the clinical picture suggests.

Management of a Blood Clotting Disorder 

Management has two arms that run in parallel: treat the underlying cause, and prevent or control bleeding or clotting episodes.

General Principles

• Treat the cause. Vitamin K for deficiency. Source control and antibiotics for septic DIC. Stop heparin in HIT. Manage liver disease.
• Replace what's missing. Factor concentrates for hemophilias, vWF concentrates for vWD, fresh frozen plasma and cryoprecipitate for multi-factor deficiencies and DIC.
• Modulate the system. Emicizumab in hemophilia A. Antifibrinolytics like tranexamic acid for mucosal bleeding. Bypassing agents (recombinant activated factor VII, activated prothrombin complex concentrate) when inhibitors block standard factor replacement.
• Anticoagulate when needed. DOACs are currently first-line for most VTE prevention and treatment. However, the next frontier in anticoagulation involves Factor XI/XIa inhibitors (e.g., asundexian, milvexian, abelacimab). Currently in late-stage trials, these agents aim to uncouple thrombosis from hemostasis by blocking pathological clot growth without significantly impairing the body's ability to seal injuries. This mechanism potentially lowers bleeding risks far below those of traditional DOACs and warfarin [15]. Warfarin retains a niche role for triple-positive APS and mechanical heart valves.
• Lifestyle and counseling. Helmet use and avoidance of contact sports for severe hemophilia. Long-haul travel precautions for thrombophilia carriers. Genetic counseling for families.

Specific Treatment Summary

• Hemophilia A: Factor VIII replacement (standard or extended half-life), emicizumab subcutaneously [6], gene therapy (valoctocogene roxaparvovec) where available [5].
• Hemophilia B: Factor IX replacement, gene therapy (etranacogene dezaparvovec) [4].
• Von Willebrand disease: Desmopressin, vWF concentrate, tranexamic acid, hormonal therapy for menorrhagia [2].
• Vitamin K deficiency / HDN: Vitamin K supplementation; prophylactic IM vitamin K at birth.
• Liver disease bleeding: Targeted blood products; treat the liver disease.
• DIC: Treat the cause; supportive blood products [1].
• Antiphospholipid syndrome: Long-term anticoagulation; LMWH plus aspirin in pregnancy [9,10].
• HIT: Stop heparin; non-heparin anticoagulant [11].
• Inherited thrombophilias: Targeted anticoagulation after events; usually no treatment in asymptomatic carriers.

Frequently Asked Questions (FAQs)

What is a blood clotting disorder?

A blood clotting disorder is a condition in which the body either clots too little, causing abnormal bleeding, or clots too much, causing dangerous clots in veins or arteries. Examples include hemophilia A and B, von Willebrand disease, factor V Leiden, antiphospholipid syndrome, and disseminated intravascular coagulation (DIC). Disorders may be inherited (present from birth) or acquired (developing later in life from liver disease, vitamin K deficiency, severe infection, or medication side effects).

What are the warning signs of a blood clotting disorder?

Bleeding-type clotting disorders cause easy bruising, prolonged bleeding from minor cuts, frequent nosebleeds, bleeding gums, heavy menstrual periods, bloody stools or urine, and joint swelling from internal bleeding. Thrombosis-type clotting disorders cause leg pain and swelling (deep vein thrombosis), sudden chest pain or shortness of breath (pulmonary embolism), stroke symptoms, or repeated miscarriages. See a clinician promptly if any of these occur, especially if there is a family history of clotting problems.

How is a blood clotting disorder diagnosed?

Diagnosis combines a detailed personal and family bleeding history with laboratory tests. Standard tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), platelet count, fibrinogen, and D-dimer. Abnormal results trigger more specific tests, such as factor VIII or IX activity for hemophilia, von Willebrand factor antigen and activity assays for vWD, and antiphospholipid antibody panels for APS. Genetic testing confirms inherited disorders like factor V Leiden or prothrombin G20210A.

Can a blood clotting disorder be cured?

Most inherited blood clotting disorders cannot be permanently cured, but many can now be controlled to allow a near-normal life. Hemophilia A and B treatment has expanded beyond intravenous factor replacement to include emicizumab (a subcutaneous antibody) and one-time AAV gene therapies approved between 2022 and 2024. Acquired clotting disorders, such as vitamin K deficiency or warfarin overdose, often resolve fully once the underlying cause is corrected.

Are blood clotting disorders inherited?

Some are, and some are not. Hemophilia A and B, most types of von Willebrand disease, factor V Leiden, prothrombin G20210A, and deficiencies of protein C, protein S, and antithrombin are all inherited. Other clotting disorders develop during life from liver disease, severe infection (causing DIC), pregnancy, certain cancers, medications such as warfarin or heparin, or autoimmune diseases such as antiphospholipid syndrome. A family history of unusual bleeding or clotting is a strong reason to ask about genetic testing.

Can a blood clotting disorder cause miscarriage?

Yes. Antiphospholipid syndrome (APS) is the most established cause; antibodies in APS trigger clots in the placenta's small vessels, cutting off oxygen and nutrients to the fetus. Inherited thrombophilias can also raise risk in some cases. Pregnant patients with a known clotting disorder or recurrent miscarriage are typically managed by a hematologist and obstetrician together, often with low-dose aspirin and low-molecular-weight heparin during pregnancy.

Glossary of Related Medical Terms

• Coagulation cascade: The chain of clotting-factor reactions that ends with fibrin forming a stable clot.
• Cell-based model of coagulation: The modern view of clotting, which happens in three steps on cell surfaces: initiation, amplification, and propagation.
• Hemostasis: The body's overall process of stopping bleeding. Includes vasoconstriction, platelet plug, clotting factors, and clot breakdown.
• Primary hemostasis: The platelet plug stage of stopping bleeding.
• Secondary hemostasis: The clotting-factor stage that builds a fibrin mesh over the platelet plug.
• Fibrinolysis: Breakdown of a blood clot once a wound has healed, mainly by the enzyme plasmin.
• Clotting factor: A plasma protein (mostly made in the liver) that helps blood clot. Factors are numbered I through XIII.
• Fibrinogen (factor I): A soluble plasma protein that thrombin converts into fibrin, the mesh of a clot.
• Thrombin (factor IIa): The central enzyme of clotting; converts fibrinogen into fibrin.
• Prothrombin time (PT) / INR: A blood test that measures the extrinsic and common pathways. INR standardizes PT results across labs.
• Activated partial thromboplastin time (aPTT): A blood test that measures the intrinsic and common pathways.
• D-dimer: A breakdown product of fibrin; elevated when clots are being formed and broken down (e.g., in DIC, DVT, PE).
• Thrombosis: Formation of a blood clot inside a healthy blood vessel where it shouldn't be.
• Thrombophilia: A tendency to form clots, either inherited or acquired.
• Hemophilia A / B: X-linked bleeding disorders caused by factor VIII (A) or factor IX (B) deficiency.
• Von Willebrand disease (vWD): The most common inherited bleeding disorder, caused by reduced or faulty von Willebrand factor.
• Desmopressin (DDAVP): A medication that releases stored von Willebrand factor and factor VIII from blood-vessel walls.
• Factor replacement therapy: Intravenous infusion of the missing clotting factor (e.g., recombinant factor VIII for hemophilia A).
• Emicizumab: An injectable bispecific antibody that mimics factor VIII's bridging function in hemophilia A.
• Bypassing agents: Drugs (e.g., recombinant activated factor VII, activated prothrombin complex concentrate) used when antibodies block the missing factor's replacement.
• AAV gene therapy: A one-time infusion that uses a harmless virus to deliver a working copy of the clotting-factor gene to liver cells.
• DIC (disseminated intravascular coagulation): A serious acquired disorder in which clotting is activated everywhere at once, using up platelets and factors, causing both clotting and bleeding.
• Antiphospholipid syndrome (APS): An autoimmune disorder in which antibodies against phospholipids drive clotting and pregnancy complications.
• Factor V Leiden: A common gene variant that makes factor V resistant to breakdown, raising clot risk.
• DOAC (direct oral anticoagulant): Newer oral blood thinners (apixaban, rivaroxaban, dabigatran, edoxaban) that target specific clotting factors.
• Heparin-induced thrombocytopenia (HIT): An immune reaction to heparin that paradoxically causes clotting, not bleeding.

Disclaimer: This article is intended for educational and informational purposes only. It is not intended to be a substitute for informed professional medical advice, diagnosis, or treatment. While the information presented here is derived from credible medical sources and is believed to be accurate and up-to-date, it is not guaranteed to be complete or error-free. See additional information.

References

1. Iba, T., Levy, J. H., Maier, C. L., Helms, J., Umemura, Y., Moore, H., Othman, M., Thachil, J., Connors, J. M., Levi, M., & Scarlatescu, E. (2025). Updated definition and scoring of disseminated intravascular coagulation in 2025: communication from the ISTH SSC Subcommittee on Disseminated Intravascular Coagulation. Journal of thrombosis and haemostasis : JTH, 23(7), 2356–2362. https://doi.org/10.1016/j.jtha.2025.03.038.
2. Connell, N. T., Flood, V. H., Brignardello-Petersen, R., Abdul-Kadir, R., Arapshian, A., Couper, S., Grow, J. M., Kouides, P., Laffan, M., Lavin, M., Leebeek, F. W. G., O'Brien, S. H., Ozelo, M. C., Tosetto, A., Weyand, A. C., James, P. D., Kalot, M. A., Husainat, N., & Mustafa, R. A. (2021). ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood advances, 5(1), 301–325. https://doi.org/10.1182/bloodadvances.2020003264
3. James, P. D., Connell, N. T., Ameer, B., Di Paola, J., Eikenboom, J., Giraud, N., Haberichter, S., Jacobs-Pratt, V., Konkle, B., McLintock, C., McRae, S., R Montgomery, R., O'Donnell, J. S., Scappe, N., Sidonio, R., Flood, V. H., Husainat, N., Kalot, M. A., & Mustafa, R. A. (2021). ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood advances, 5(1), 280–300. https://doi.org/10.1182/bloodadvances.2020003265
4. Anguela, X. M., & High, K. A. (2024). Hemophilia B and gene therapy: a new chapter with etranacogene dezaparvovec. Blood advances, 8(7), 1796–1803. https://doi.org/10.1182/bloodadvances.2023010511
5. Samelson-Jones, B. J., Small, J. C., & George, L. A. (2024). Roctavian gene therapy for hemophilia A. Blood advances, 8(19), 5179–5189. https://doi.org/10.1182/bloodadvances.2023011847
6. Alcedo Andrade, P. E., Mannucci, P. M., & Kessler, C. M. (2024). Emicizumab: the hemophilia A game-changer. Haematologica, 109(5), 1334–1347. https://doi.org/10.3324/haematol.2022.282099
7. Srivastava, A., Santagostino, E., Dougall, A., Kitchen, S., Sutherland, M., Pipe, S. W., Carcao, M., Mahlangu, J., Ragni, M. V., Windyga, J., Llinás, A., Goddard, N. J., Mohan, R., Poonnoose, P. M., Feldman, B. M., Lewis, S. Z., van den Berg, H. M., Pierce, G. F., & WFH Guidelines for the Management of Hemophilia panelists and co-authors (2020). WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia : the official journal of the World Federation of Hemophilia, 26 Suppl 6, 1–158. https://doi.org/10.1111/hae.14046
8. Castaman, G., & Linari, S. (2017). Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders. Journal of clinical medicine, 6(4), 45. https://doi.org/10.3390/jcm6040045
9. Garcia, D., & Erkan, D. (2018). Diagnosis and Management of the Antiphospholipid Syndrome. The New England journal of medicine, 378(21), 2010–2021. https://doi.org/10.1056/NEJMra1705454
10. Tektonidou, M. G., Andreoli, L., Limper, M., et al. (2019). EULAR recommendations for the management of antiphospholipid syndrome in adults. Annals of the Rheumatic Diseases, 78(10), 1296–1304. https://doi.org/10.1136/annrheumdis-2019-215213
11. Cuker, A., Arepally, G. M., Chong, B. H., Cines, D. B., Greinacher, A., Gruel, Y., Linkins, L. A., Rodner, S. B., Selleng, S., Warkentin, T. E., Wex, A., Mustafa, R. A., Morgan, R. L., & Santesso, N. (2018). American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood advances, 2(22), 3360–3392. https://doi.org/10.1182/bloodadvances.2018024489
12. U.S. Food and Drug Administration. (2024). FDA Approves Pfizer's HYMPAVZI (marstacimab-hncq) for the Treatment of Adults and Adolescents with Hemophilia A or B Without Inhibitors. FDA Press Release / October 2024.
13. BioMarin Pharmaceutical Inc. (2024). BioMarin Announces Strategic Realignment of ROCTAVIAN (valoctocogene roxaparvovec-rvox) Commercial Focus to the United States. Business Wire.
14. U.S. Food and Drug Administration. (2024). FDA Approves Pfizer's BEQVEZ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. FDA Press Release / April 2024.
15. Hsu, C., Hutt, E., Bloomfield, D. M., Gailani, D., & Weitz, J. I. (2021). Factor XI Inhibition to Uncouple Thrombosis From Hemostasis: JACC Review Topic of the Week. Journal of the American College of Cardiology, 78(6), 625–631. https://doi.org/10.1016/j.jacc.2021.06.010
16. Northup, P. G., Garcia-Pagan, J. C., Garcia-Tsao, G., Intagliata, N. M., Superina, R. A., Roberts, L. N., Lisman, T., & Valla, D. C. (2021). Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology (Baltimore, Md.), 73(1), 366–413. https://doi.org/10.1002/hep.31646
17. Key, N. S., Khorana, A. A., Kuderer, N. M., Bohlke, K., Lee, A. Y. Y., Arcelus, J. I., Wong, S. L., Balaban, E. P., Flowers, C. R., Gates, L. E., Kakkar, A. K., Tempero, M. A., Gupta, S., Lyman, G. H., & Falanga, A. (2023). Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 41(16), 3063–3071. https://doi.org/10.1200/JCO.23.00294