Mod 2.3 Bleeding
Recall
HEMOSTASIS Hemostasis Definition:
● Hemostasis is a dynamic process that stops bleeding. It involves interactions between platelets and
the blood vessel wall.
Platelet Activation:
● Platelets are activated when they adhere to von Willebrand factor (VWF) and collagen at the site of
vessel injury.
● Blood flow (shear forces) and the inflammatory state of the endothelium also contribute to platelet
activation, especially in areas with diseased vessel walls.
Role of Activated Platelets in Coagulation:
● The activated platelet surface serves as a major site for coagulation factor activation.
● This leads to further platelet activation and fibrin formation, crucial for stabilizing the blood clot.
Genetic and Acquired Influences:
● Both genetic and acquired factors affecting platelets, blood vessel walls, and the coagulation and
fibrinolytic systems can result in normal hemostasis or disorders like bleeding or thrombosis (clot
formation).
Platelet Production:
● Platelets are derived from megakaryocytes in the bone marrow.
● The normal platelet count is 150,000–450,000/μL.
● Thrombopoietin (TPO), mainly synthesized in the liver, regulates platelet production.
● Inflammatory signals, particularly interleukin-6, increase TPO synthesis.
● TPO binds to its receptor on platelets and megakaryocytes, promoting platelet production when
platelet levels are low.
Platelet Life Span and Distribution:
● Platelets have an average life span of 7–10 days.
● About one-third of circulating platelets are stored in the spleen, and this fraction increases with
splenic enlargement.
Endothelium's Role in Thrombosis Prevention:
● Healthy vascular endothelium prevents thrombosis by inhibiting platelet function.
● When the endothelium is damaged, these inhibitory effects are lost, and platelets adhere to the
exposed subendothelial matrix through VWF.
Platelet Adhesion and Aggregation:
● Adhesion triggers intracellular signals that activate glycoprotein (Gp) IIb/IIIa (αIIbβ3) receptors on
platelets, leading to aggregation.
● Activated platelets release granules containing nucleotides, adhesive proteins, growth factors, and
procoagulants that promote clot formation and stabilize the clot.
Formation of Platelet Thrombus:
● Platelet aggregation recruits more platelets to the injury site.
● This leads to the formation of an occlusive platelet thrombus, which is stabilized by a fibrin mesh
produced by the coagulation cascade.
, APPROACH TO PATIENT
(Harrison’s Principles of Internal Medicine 20th and 21st ed, Chapter 115)
APPROACH TO PATIENT WITH BLEEDING Approach to the Patient: Bleeding and Thrombosis
AND THROMBOSIS
Clinical Presentation
● Hemostasis Disorders: Can be either inherited or acquired.
○ Family and Personal History: Key for determining chronicity and likelihood of inherited disorders.
○ Etiology Clues: Based on bleeding or thrombosis site and possible triggers (medical conditions,
medications, supplements).
History of Bleeding
● Predictor of Bleeding Risk: A history of spontaneous or trauma/surgery-induced bleeding is crucial.
○ Hemarthroses: Characteristic of factor VIII or IX deficiencies (moderate to severe).
○ Mucosal Bleeding: Suggests platelet disorders or von Willebrand disease (VWD).
● Bleeding Score: Tool for predicting type 1 VWD; self-administered forms are validated for screening and
avoiding unnecessary testing.
● Common Bleeding Symptoms:
○ Prolonged Bleeding: Post-surgery, dental procedures, trauma, heavy menstrual bleeding (HMB),
postpartum hemorrhage.
○ Large Bruises: Often with lumps.
● Other Conditions Mimicking Coagulopathy:
○ Ehlers-Danlos Syndrome: Joint hyperextensibility and post-traumatic bleeding.
○ Cushing’s Syndrome, Aging, Steroid Use: Skin changes leading to easy bruising (senile
purpura).
● Epistaxis (Nosebleeds):
○ Common in children but may indicate a bleeding disorder, particularly in hereditary hemorrhagic
telangiectasia and boys with VWD.
● Heavy Menstrual Bleeding (HMB):
○ Definition: Loss >80 mL per cycle.
○ Predictors: Iron deficiency anemia, blood transfusions, clot passage, frequent pad/tampon
changes.
○ Associated Disorders: VWD, factor XI deficiency, platelet function disorders, and hemophilia.
● Postpartum Hemorrhage: Common in VWD or hemophilia A; delayed in some due to factor normalization
during pregnancy.
● Tonsillectomy and Surgery Risks: Hemostatic challenges; delayed bleeding after tonsillectomy or
colonic polyp resection.
● Hemarthroses & Spontaneous Muscle Hematomas: Typically seen in congenital factor VIII or IX
deficiencies and occasionally in other clotting factor deficiencies.
Prohemorrhagic Effects of Medications & Supplements
● Aspirin & NSAIDs: Inhibit cyclooxygenase, impair primary hemostasis, and can unmask underlying
bleeding disorders.
● Herbal Supplements: Some, like fish oil and vitamin E, impair platelet function and can exacerbate
, bleeding.
Systemic Diseases & Bleeding
● Acquired Bleeding Disorders: May result from liver disease, renal impairment, hypothyroidism, bone
marrow failure, or vitamin K deficiency.
● Thrombocytopenia: Bleeding risk increases when platelet count is <50,000/µL.
History of Thrombosis
● Risk Factors:
○ Arterial Thrombosis: Primarily related to atherosclerosis.
○ Venous Thrombosis: Linked to immobility, surgery, malignancy, hormonal therapy, obesity, and
genetic factors.
● Idiopathic Venous Thromboembolism (VTE): Strong predictor of recurrence.
Laboratory Evaluation
● No Global Hemostasis Test: Clinical assessment is essential.
● Coagulation Tests:
○ PT (Prothrombin Time): Assesses factors I, II, V, VII, X.
○ INR (International Normalized Ratio): Adjusts for variability in PT results.
○ aPTT (Activated Partial Thromboplastin Time): Assesses factors XI, IX, VIII, X, V, II, fibrinogen,
and others.
● Limitations of Screening Tests:
○ PFA-100: More specific for VWD but insufficient for mild disorders.
○ Thromboelastography: Useful intraoperatively but limited in broader hemostasis/thrombosis
diagnosis.
● Preoperative Testing:
○ Abnormal PT: Detects unrecognized liver disease or vitamin K deficiency.
○ aPTT: Less useful unless there’s a relevant history or risk factor.
Additional Considerations
● Blood Sample Handling: Proper handling is crucial to avoid false results in coagulation assays.
● Thrombophilia Testing: Should be limited to cases where results would influence management.
Mixing Studies
● Purpose: To evaluate a prolonged activated partial thromboplastin time (aPTT) or prothrombin time (PT)
and differentiate between a factor deficiency and an inhibitor.
● Process: Patient plasma is mixed with normal plasma in a 1:1 ratio, and aPTT or PT is measured
immediately and after incubation at 37°C (usually for 30, 60, or 120 minutes).
○ Factor Deficiency: aPTT corrects with mixing and remains corrected after incubation.
○ Lupus Anticoagulant: No correction occurs after mixing or incubation.
○ Acquired Factor Inhibitors (e.g., Factor VIII Inhibitor): May initially correct but prolongs or
remains prolonged after incubation.
○ Other Causes: Failure to correct can also result from heparin, fibrin split products, paraproteins, or
other inhibitors.
Recall
HEMOSTASIS Hemostasis Definition:
● Hemostasis is a dynamic process that stops bleeding. It involves interactions between platelets and
the blood vessel wall.
Platelet Activation:
● Platelets are activated when they adhere to von Willebrand factor (VWF) and collagen at the site of
vessel injury.
● Blood flow (shear forces) and the inflammatory state of the endothelium also contribute to platelet
activation, especially in areas with diseased vessel walls.
Role of Activated Platelets in Coagulation:
● The activated platelet surface serves as a major site for coagulation factor activation.
● This leads to further platelet activation and fibrin formation, crucial for stabilizing the blood clot.
Genetic and Acquired Influences:
● Both genetic and acquired factors affecting platelets, blood vessel walls, and the coagulation and
fibrinolytic systems can result in normal hemostasis or disorders like bleeding or thrombosis (clot
formation).
Platelet Production:
● Platelets are derived from megakaryocytes in the bone marrow.
● The normal platelet count is 150,000–450,000/μL.
● Thrombopoietin (TPO), mainly synthesized in the liver, regulates platelet production.
● Inflammatory signals, particularly interleukin-6, increase TPO synthesis.
● TPO binds to its receptor on platelets and megakaryocytes, promoting platelet production when
platelet levels are low.
Platelet Life Span and Distribution:
● Platelets have an average life span of 7–10 days.
● About one-third of circulating platelets are stored in the spleen, and this fraction increases with
splenic enlargement.
Endothelium's Role in Thrombosis Prevention:
● Healthy vascular endothelium prevents thrombosis by inhibiting platelet function.
● When the endothelium is damaged, these inhibitory effects are lost, and platelets adhere to the
exposed subendothelial matrix through VWF.
Platelet Adhesion and Aggregation:
● Adhesion triggers intracellular signals that activate glycoprotein (Gp) IIb/IIIa (αIIbβ3) receptors on
platelets, leading to aggregation.
● Activated platelets release granules containing nucleotides, adhesive proteins, growth factors, and
procoagulants that promote clot formation and stabilize the clot.
Formation of Platelet Thrombus:
● Platelet aggregation recruits more platelets to the injury site.
● This leads to the formation of an occlusive platelet thrombus, which is stabilized by a fibrin mesh
produced by the coagulation cascade.
, APPROACH TO PATIENT
(Harrison’s Principles of Internal Medicine 20th and 21st ed, Chapter 115)
APPROACH TO PATIENT WITH BLEEDING Approach to the Patient: Bleeding and Thrombosis
AND THROMBOSIS
Clinical Presentation
● Hemostasis Disorders: Can be either inherited or acquired.
○ Family and Personal History: Key for determining chronicity and likelihood of inherited disorders.
○ Etiology Clues: Based on bleeding or thrombosis site and possible triggers (medical conditions,
medications, supplements).
History of Bleeding
● Predictor of Bleeding Risk: A history of spontaneous or trauma/surgery-induced bleeding is crucial.
○ Hemarthroses: Characteristic of factor VIII or IX deficiencies (moderate to severe).
○ Mucosal Bleeding: Suggests platelet disorders or von Willebrand disease (VWD).
● Bleeding Score: Tool for predicting type 1 VWD; self-administered forms are validated for screening and
avoiding unnecessary testing.
● Common Bleeding Symptoms:
○ Prolonged Bleeding: Post-surgery, dental procedures, trauma, heavy menstrual bleeding (HMB),
postpartum hemorrhage.
○ Large Bruises: Often with lumps.
● Other Conditions Mimicking Coagulopathy:
○ Ehlers-Danlos Syndrome: Joint hyperextensibility and post-traumatic bleeding.
○ Cushing’s Syndrome, Aging, Steroid Use: Skin changes leading to easy bruising (senile
purpura).
● Epistaxis (Nosebleeds):
○ Common in children but may indicate a bleeding disorder, particularly in hereditary hemorrhagic
telangiectasia and boys with VWD.
● Heavy Menstrual Bleeding (HMB):
○ Definition: Loss >80 mL per cycle.
○ Predictors: Iron deficiency anemia, blood transfusions, clot passage, frequent pad/tampon
changes.
○ Associated Disorders: VWD, factor XI deficiency, platelet function disorders, and hemophilia.
● Postpartum Hemorrhage: Common in VWD or hemophilia A; delayed in some due to factor normalization
during pregnancy.
● Tonsillectomy and Surgery Risks: Hemostatic challenges; delayed bleeding after tonsillectomy or
colonic polyp resection.
● Hemarthroses & Spontaneous Muscle Hematomas: Typically seen in congenital factor VIII or IX
deficiencies and occasionally in other clotting factor deficiencies.
Prohemorrhagic Effects of Medications & Supplements
● Aspirin & NSAIDs: Inhibit cyclooxygenase, impair primary hemostasis, and can unmask underlying
bleeding disorders.
● Herbal Supplements: Some, like fish oil and vitamin E, impair platelet function and can exacerbate
, bleeding.
Systemic Diseases & Bleeding
● Acquired Bleeding Disorders: May result from liver disease, renal impairment, hypothyroidism, bone
marrow failure, or vitamin K deficiency.
● Thrombocytopenia: Bleeding risk increases when platelet count is <50,000/µL.
History of Thrombosis
● Risk Factors:
○ Arterial Thrombosis: Primarily related to atherosclerosis.
○ Venous Thrombosis: Linked to immobility, surgery, malignancy, hormonal therapy, obesity, and
genetic factors.
● Idiopathic Venous Thromboembolism (VTE): Strong predictor of recurrence.
Laboratory Evaluation
● No Global Hemostasis Test: Clinical assessment is essential.
● Coagulation Tests:
○ PT (Prothrombin Time): Assesses factors I, II, V, VII, X.
○ INR (International Normalized Ratio): Adjusts for variability in PT results.
○ aPTT (Activated Partial Thromboplastin Time): Assesses factors XI, IX, VIII, X, V, II, fibrinogen,
and others.
● Limitations of Screening Tests:
○ PFA-100: More specific for VWD but insufficient for mild disorders.
○ Thromboelastography: Useful intraoperatively but limited in broader hemostasis/thrombosis
diagnosis.
● Preoperative Testing:
○ Abnormal PT: Detects unrecognized liver disease or vitamin K deficiency.
○ aPTT: Less useful unless there’s a relevant history or risk factor.
Additional Considerations
● Blood Sample Handling: Proper handling is crucial to avoid false results in coagulation assays.
● Thrombophilia Testing: Should be limited to cases where results would influence management.
Mixing Studies
● Purpose: To evaluate a prolonged activated partial thromboplastin time (aPTT) or prothrombin time (PT)
and differentiate between a factor deficiency and an inhibitor.
● Process: Patient plasma is mixed with normal plasma in a 1:1 ratio, and aPTT or PT is measured
immediately and after incubation at 37°C (usually for 30, 60, or 120 minutes).
○ Factor Deficiency: aPTT corrects with mixing and remains corrected after incubation.
○ Lupus Anticoagulant: No correction occurs after mixing or incubation.
○ Acquired Factor Inhibitors (e.g., Factor VIII Inhibitor): May initially correct but prolongs or
remains prolonged after incubation.
○ Other Causes: Failure to correct can also result from heparin, fibrin split products, paraproteins, or
other inhibitors.
