Thrombosis syndromes (hypercoagulability): Pathology review


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Thrombosis syndromes (hypercoagulability): Pathology review

Hematological system


Iron deficiency anemia



Sideroblastic anemia

Anemia of chronic disease

Lead poisoning

Hemolytic disease of the newborn

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Autoimmune hemolytic anemia

Pyruvate kinase deficiency

Paroxysmal nocturnal hemoglobinuria

Sickle cell disease (NORD)

Hereditary spherocytosis

Anemia of chronic disease

Aplastic anemia

Fanconi anemia

Megaloblastic anemia

Folate (Vitamin B9) deficiency

Vitamin B12 deficiency

Fanconi anemia

Diamond-Blackfan anemia

Heme synthesis disorders

Acute intermittent porphyria

Porphyria cutanea tarda

Lead poisoning

Coagulation disorders


Vitamin K deficiency

Platelet disorders

Bernard-Soulier syndrome

Glanzmann's thrombasthenia

Hemolytic-uremic syndrome

Immune thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Mixed platelet and coagulation disorders

Von Willebrand disease

Disseminated intravascular coagulation

Heparin-induced thrombocytopenia

Thrombosis syndromes (hypercoagulability)

Antithrombin III deficiency

Factor V Leiden

Protein C deficiency

Protein S deficiency

Antiphospholipid syndrome


Hodgkin lymphoma

Non-Hodgkin lymphoma


Chronic leukemia

Acute leukemia

Leukemoid reaction

Leukemoid reaction

Dysplastic and proliferative disorders

Myelodysplastic syndromes

Polycythemia vera (NORD)

Myelofibrosis (NORD)

Essential thrombocythemia (NORD)

Langerhans cell histiocytosis

Mastocytosis (NORD)

Plasma cell dyscrasias

Multiple myeloma

Monoclonal gammopathy of undetermined significance

Waldenstrom macroglobulinemia

Hematological system pathology review

Microcytic anemia: Pathology review

Non-hemolytic normocytic anemia: Pathology review

Intrinsic hemolytic normocytic anemia: Pathology review

Extrinsic hemolytic normocytic anemia: Pathology review

Macrocytic anemia: Pathology review

Heme synthesis disorders: Pathology review

Coagulation disorders: Pathology review

Platelet disorders: Pathology review

Mixed platelet and coagulation disorders: Pathology review

Thrombosis syndromes (hypercoagulability): Pathology review

Lymphomas: Pathology review

Leukemias: Pathology review

Plasma cell disorders: Pathology review

Myeloproliferative disorders: Pathology review


Thrombosis syndromes (hypercoagulability): Pathology review

USMLE® Step 1 questions

0 / 6 complete


USMLE® Step 1 style questions USMLE

of complete

A 52-year-old woman, para 4 gravida 2 aborta 2, comes to the clinic for a follow-up appointment after a hospitalization. Two weeks ago, she had an incident of acute, severe abdominal pain and bloody stools. She was diagnosed with portal vein thrombosis. She denies similar episodes in the past. Medical history is notable for Legg-Calvé-Perthes disease as a child. She does not smoke, drink excessive alcohol, or use illicit drugs. She had 2 spontaneous abortions in the first trimester, following 2 successful pregnancies. Family history is remarkable for DVT in her maternal uncle and colon cancer in her father. The physician suspects an inherited condition. Which of the following will prompt further evaluation in this patient?  


Content Reviewers

Yifan Xiao, MD

Antonia Syrnioti, MD


Megan Gullotto, MSMI

Maria Emfietzoglou, MD

Sam Gillespie, BSc

Tanner Marshall, MS

At the emergency department, a 30 year old Caucasian female named Celia came in with pain and swelling in her right calf. She has a history of pregnancy loss and her mother has a history of recurrent episodes of venous thromboembolism. Her medical history is otherwise unremarkable. Coagulation studies show normal PTT. Next to Celia, there’s a 60 year old male called Nicholas who developed a painful lesion on his arm after starting anticoagulation therapy with warfarin. Now, there’s also a 26 year old African American female named Mary who has recurrent pregnancy losses. She was diagnosed with systemic lupus erythematosus about a year ago. She has no family history of thrombophilic disorder.

All of them suffer from thrombophilic disorders, or thrombosis syndromes, which are inherited or acquired diseases that predispose an individual to clot formation. Inherited disorders include factor V Leiden, prothrombin gene mutation, protein C and S deficiency, and antithrombin III deficiency, while the most important acquired disorder is antiphospholipid antibody syndrome. But before going into the individual thrombophilic disorders, let’s go through the normal coagulation system. The coagulation pathway is divided into an extrinsic and an intrinsic pathway, which join into a common pathway that ultimately result in the formation of fibrin clots. The extrinsic pathway starts when trauma damages a blood vessel, and exposes the cells under the endothelial layer, which have tissue factor in their membrane. Activated factor VII binds to tissue factor, forming a complex that then binds to and activates factor X. The intrinsic pathway starts when a circulating factor XII, activates factor XI, which then activates factor IX. Finally, factor IX forms a complex with factor VIII, and this complex binds to and activates factor X. In the common pathway. Activated factor X activates factor V, which converts prothrombin, or factor II, into thrombin. Thrombin then converts fibrinogen, or factor I, into fibrin, which cross-links to form a fibrin mesh that stabilizes the platelet plug. Now, prothrombin time, or PT assesses the extrinsic and common coagulation pathways, and partial thromboplastin time, or PTT assess the intrinsic and common coagulation pathways. Alright, but in order to prevent over-coagulation, the liver makes proteins C and S, which are vitamin K-dependent anticoagulant factors. In the presence of protein S as a cofactor, protein C acts by enzymatically inactivating factors V and VIII. Finally, a protein called antithrombin III inhibits factor X and factor II.


Thrombosis syndromes, also known as hypercoagulability, are a group of disorders characterized by an increased tendency to develop blood clots. These disorders can be inherited or acquired, and they can affect different parts of the body, including the veins and arteries. Thrombosis syndromes can be inherited, like factor V Leiden, prothrombin gene mutation, protein C and S deficiency, antithrombin III deficiency, or acquired like antiphospholipid syndrome.

Diagnosis can be made based on clinical presentation, coagulation studies, more specific lab tests like ELISA for antiphospholipid antibodies, as well as genetic testing to detect the specific mutations. Treatment involves a combination of anticoagulant therapy, lifestyle modifications, and management of the underlying conditions. Anticoagulant medications, such as warfarin and heparin, can help prevent blood clots from forming or growing.


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  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
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  5. "Technical standards and guidelines: Venous thromboembolism (Factor V Leiden and prothrombin 20210G>A testing): A disease-specific supplement to the standards and guidelines for clinical genetics laboratories" Genetics in Medicine (2005)
  6. "Laboratory Diagnostics in Thrombophilia" Hämostaseologie (2019)
  7. "Antiphospholipid Syndrome" Progress in Cardiovascular Diseases (2009)
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