What are examples of coagulopathy?

Examples of Coagulopathy

Coagulopathies are broadly classified into inherited and acquired disorders, with the most common inherited forms being hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), and von Willebrand disease, while the most common acquired forms are disseminated intravascular coagulation (DIC), liver disease, and vitamin K deficiency. 1, 2

Inherited Coagulopathies

Most Common Inherited Disorders

• Hemophilia A (Factor VIII deficiency) is the most common severe inherited coagulation disorder, transmitted as an X-linked recessive trait, causing delayed deep bleeding into muscles and joints 3, 2, 4
• Hemophilia B (Factor IX deficiency) is clinically indistinguishable from hemophilia A and also follows X-linked recessive inheritance 3, 4
• Von Willebrand disease is the most common inherited coagulopathy overall, manifesting with mucocutaneous bleeding including easy bruising, epistaxis, menorrhagia, and prolonged bleeding after dental or surgical procedures 3, 4

Thrombophilic Inherited Disorders

• Protein C and S deficiencies are inherited as autosomal dominant traits and lead to increased risk of venous thrombosis, including cerebral venous thrombosis 1, 5
• Factor V Leiden mutation increases thrombotic risk, particularly in younger patients, and is associated with venous rather than arterial thrombosis 1, 5
• Prothrombin G20210A mutation similarly increases venous thrombotic risk 5
• Antithrombin III deficiency represents a major inherited thrombophilic risk factor 5

Critical caveat: These inherited thrombophilic disorders have NOT been strongly associated with arterial events such as myocardial infarction or ischemic stroke, despite their clear association with venous thromboembolism 1

Rare Inherited Bleeding Disorders

• Inherited disorders of clotting factors V, VII, X, XI, and XIII are autosomal recessive traits that can lead to cerebral hemorrhage in childhood or the neonatal period 1
• These rare factor deficiencies may only become clinically evident in homozygotes or compound heterozygotes 4

Acquired-Appearing Inherited Disorders

• Lupus anticoagulant and anticardiolipin antibodies can be familial in approximately 10% of cases, despite appearing to be acquired 1
• Paradoxically, lupus anticoagulant predisposes to thrombosis rather than bleeding 6

Acquired Coagulopathies

Most Common Acquired Disorders

• Disseminated intravascular coagulation (DIC) is characterized by intravascular activation of coagulation with loss of localization, causing damage to microvasculature and potential organ dysfunction 1, 2
• Liver disease causes coagulopathy through multiple mechanisms including decreased synthesis of coagulation factors, but paradoxically can also create a hypercoagulable state due to elevated factor VIII and von Willebrand factor with decreased protein C 1, 7, 6
• Vitamin K deficiency leads to decreased production of factors II, VII, IX, and X 6, 2

Disseminated Intravascular Coagulation Subtypes

DIC associated with cancer should be categorized into three clinically distinct subtypes: 1

• Procoagulant DIC presents with thrombosis (arterial ischemia, venous thromboembolism), commonly seen with pancreatic cancer and adenocarcinomas 1
• Hyperfibrinolytic DIC presents with widespread bleeding, classically seen in acute promyelocytic leukemia and metastatic prostate cancer 1
• Subclinical DIC shows laboratory markers of coagulation activation without obvious clinical manifestations 1

The ISTH overt-DIC diagnostic criteria include: decreased platelet count, prolonged prothrombin time, increased fibrin-related markers, and decreased fibrinogen, though notably these criteria do not include endothelium-related markers despite endothelial injury being essential to the DIC definition 1

Liver Disease Coagulopathy

Cirrhotic patients exhibit a paradoxical hypercoagulable state despite abnormal coagulation tests: 7

• Elevated factor VIII and von Willebrand factor coupled with decreased protein C drive hypercoagulability 7
• Traditional coagulation tests (PT/INR, aPTT) fail to capture this hypercoagulable state as they only measure procoagulant factors 7
• Critical pitfall: Do not rely on prolonged INR as evidence of bleeding risk; it systematically underestimates coagulation capacity in cirrhosis 7
• Prophylactic anticoagulation should not be withheld based solely on abnormal coagulation tests in hospitalized cirrhotic patients 7

Massive Transfusion Coagulopathy

• Coagulopathy in trauma patients differs from elective surgery, with uncontrolled tissue trauma, variable treatment intervals, frequent hypothermia and shock, and often progression to DIC 8
• Hypocalcemia develops during massive transfusion due to citrate in blood products binding calcium, impairing fibrin polymerization and platelet function 9
• Ionized calcium should be maintained >0.9 mmol/L during massive transfusion 9

Clinical Presentation Patterns

Bleeding Patterns by Disorder Type

• Primary hemostatic disorders (platelets and von Willebrand factor) cause mucocutaneous bleeding: epistaxis, menorrhagia, petechiae, easy bruising 3
• Secondary hemostatic disorders (coagulation factor deficiencies) cause delayed, deep bleeding into muscles and joints 3

Thrombotic Presentations

• Cortical vein thrombosis presents with headaches (71%), seizures (58%), and focal neurologic deficits (62%), with mean time to diagnosis of 7 days 5
• Cancer-associated procoagulant DIC manifests as arterial ischemia with patchy skin discoloration, poor digital circulation, cerebrovascular symptoms, peripheral neuropathy, ischemic colitis, or venous thromboembolism 1

Management Principles by Coagulopathy Type

Inherited Bleeding Disorders

• Preoperative treatment with desmopressin or factor replacement is required for invasive procedures to facilitate normal hemostasis 4
• Current lab values and hematology consultation are imperative prior to invasive dental or surgical treatment 4

Acquired Coagulopathies

• Liver disease: Fresh frozen plasma (FFP) contains all coagulation components physiologically balanced and is the appropriate substitution therapy; prothrombin complex concentrates should be used only in emergencies 6
• Vitamin K deficiency: Adequate vitamin K substitution is indicated 6
• DIC: Management primarily consists of aggressive treatment of the underlying disease; substitution therapy should be carefully monitored 6
• Massive transfusion: First-line treatment should be FFP to correct decreased coagulation factor levels, with an optimal plasma:red blood cell ratio of at least 1:2 9, 8

Critical contraindication: Heparin is contraindicated in uncontrolled active bleeding states, except when due to disseminated intravascular coagulation 10