Thrombophilia (hypercoagulability)


Blood Science Mind Map on Thrombophilia (hypercoagulability), created by maisie_oj on 04/30/2013.
Mind Map by maisie_oj, updated more than 1 year ago
Created by maisie_oj almost 10 years ago

Resource summary

Thrombophilia (hypercoagulability)
  1. Introduction
    1. What is thrombophilia?
      1. Its a tendency for an individual's blood to inappropriately form thrombi (clots that occlude blood vessels) or coagulate in the wrong place + time
      2. Thrombotic disorders
        1. Arterial
          1. Myocardial infarction
            1. Stroke
              1. Peripheral arterial disease
              2. Venous
                1. DVT
                  1. Pulmonary embolism (PE)
                    1. Risk factor = oral contraceptives
                      1. Vary in size: can be small PE's all the way up to massive PE's
                        1. Symptoms vary with size (from mild cough with small PE's and pain, haemoptysis (coughing blood) and dyspnoea, fainting, sudden death with massive PEs)
                  2. Thrombosis = closure of a vessel by a thrombus (clot)
                    1. Thromboses can fragment or detach and travel in the blood to a second site
                      1. This travelling form is called an embolus (can also block a tissue vessel -> causes infarction)
                        1. Infarction = mass cell death due to the occlusion of a supplying blood vessel
                      2. Types of thrombus
                        1. Red
                          1. Mainly RBCs in fibrin mesh
                          2. White
                            1. Mainly platelets in fibrin mesh
                        2. Thrombophilia can be acquired or inherited
                        3. Factors affecting thrombosis
                          1. Prothrombotic
                            1. Vascular damage
                              1. Platelet activation
                                1. Activation of the coagulation cascade
                                2. Antithrombotic
                                  1. Normal blood flow
                                    1. Anicoagulants
                                      1. Fibrinolytic system
                                        1. Normal endothelium
                                        2. Virchow's triad
                                          1. The pathophysiology of thrombosis involves...
                                            1. Changes in the vessel wall
                                              1. Deformities can cause turbulence (see below) and damage exposes ECM
                                              2. Changes in the blood flow
                                                1. Stasis promotes contact between platelets and activated procoagulants and the vessel wall
                                                  1. Turbulent blood flow results in damage to the endothelium - exposes ECM
                                                    1. Thromboses can occur around venous valves (+++turbulence)
                                                  2. Changes in the coagulability of the blood
                                                    1. Deficiences of the natural anticoagulants; Protein C, Protein S, antithrombin(III)
                                                      1. Acquisition of anti-coagulation factors; Lupus anticoagulant (LA)
                                                    2. Important to keep this in mind with thrombosis!
                                                  3. Pathaphysiology of thrombosis
                                                    1. Blood vessel injury (endothelial damage)
                                                      1. Activation of blood coagulation (coagulation cascade)
                                                        1. Thrombin
                                                          1. Fibrin
                                                          2. +
                                                            1. Hypercoagulability of blood
                                                          3. Platelet activation by subendothelial collagen
                                                            1. Platelet factor 3
                                                              1. +
                                                              2. Thromboxane A2 (TxA2)
                                                                1. Thromboxane causes vasoconstriction
                                                                  1. Platelet activation and aggregation
                                                                    1. Platelet and fibrin mass (thrombus)
                                                                  2. ADP
                                                                  3. +
                                                                    1. Stasis / turbulence of bloodflow
                                                                      1. +
                                                                2. Causes (acquired vs. hereditary)
                                                                  1. Hereditary
                                                                    1. Antithrombin(III) deficiency
                                                                      1. Prothrombin gene mutation
                                                                        1. Protein C/S deficiency
                                                                          1. Elevated factors; XI, VIII
                                                                            1. Dysfibriginogenemia
                                                                              1. Tissue plasminogen activator inhibitor (t-PAI) defects
                                                                                1. Factor V Leiden (activated Protein C resistence)
                                                                                  1. Sticky platelet syndrome
                                                                                    1. Homocystinemia
                                                                                      1. Antiphospholipid Ab'
                                                                                        1. Antiphospholipid syndrome (primary disease; or secondary to lupus)
                                                                                          1. Risk of thrombosis - especially PE or DVT
                                                                                            1. Also causes multiple miscarriages
                                                                                        2. Acquired (risk factors)
                                                                                          1. Prolonged immobilisation (e.g. in hospitals or on long flights)
                                                                                            1. Chronic inflammatory disease
                                                                                              1. Oral contraceptives
                                                                                                1. Oestrogens
                                                                                                2. Nephrotic syndrome
                                                                                                  1. Pregnancy
                                                                                                    1. Trauma / general surgery
                                                                                                      1. Allows exposure of blood to tissue factor
                                                                                                      2. CVD
                                                                                                        1. Valve disease
                                                                                                      3. Natural anticoagulants
                                                                                                        1. Antithrombin(III)
                                                                                                          1. Activated by heparin and heparin-like molecules (e.g. heperan-sulfate)
                                                                                                            1. Function: inactivates thrombin (fIIa), fIXa, fXa and fXIa
                                                                                                            2. Protein C
                                                                                                              1. Function: decreases the generation of thrombin (fIIa) by inactivating; fVa, fVIIIa and fXa
                                                                                                                1. Vit. K dependent, requires endothelial thrombomodulin and activation by protein S
                                                                                                                  1. Deficicency: in about 4-12% of patients with thrombotic disease
                                                                                                                    1. Can be heterozygous condition (mild)
                                                                                                                      1. Can be homozygous; presents early
                                                                                                                        1. Other conditions; Protein S deficiency, mutated fV (Factor V leiden) and thrombomodulin mutation
                                                                                                                          1. Factor V Leiden = activated protein C resistence
                                                                                                                            1. Results in increased thrombin formation
                                                                                                                      2. Protein S
                                                                                                                        1. Function: Activates Protein C
                                                                                                                          1. Vit. K dependent
                                                                                                                          2. All produced in the liver
                                                                                                                          3. Hypercoagulable
                                                                                                                            1. First rule out all other risk factors (surgery, pregnancy, obesity etc.)
                                                                                                                              1. To label someone as hypercoagulable they must fit a criteria
                                                                                                                                1. First thrombosis <40yrs
                                                                                                                                  1. Recurrent thrombosis
                                                                                                                                    1. Family history
                                                                                                                                      1. Thrombosis in unusual sites (cerebral veins, hepatic veins, renal veins, mesenteric veins, inferior vena cava
                                                                                                                                        1. Plus positive lab results for any of the mentioned inherited conditions
                                                                                                                                      2. Virchow's triad: Venous vs. arterial thrombosis
                                                                                                                                        1. Venous
                                                                                                                                          1. 1) Vessel walls = normal
                                                                                                                                            1. 2) Blood flow = stasis: low-grade activaion of clotting factors and platelets -> red clots
                                                                                                                                              1. 3) Abnormalities of blood composition
                                                                                                                                                1. Normal vessel wall; flow and shear are low; clot = RBC-rich (red clot)
                                                                                                                                                  1. Risk factors = trauma/surgery and cancer
                                                                                                                                                    1. Treatment = anticoagulants
                                                                                                                                                  2. Arterial
                                                                                                                                                    1. 1) Vessel walls = atherosclerosis -> plaque ruptures -> exposes tissue factor -> clotting cascade -> white clot
                                                                                                                                                      1. 2) Blood flow = turbulence (high shear)
                                                                                                                                                        1. 3) Abnormalities of blood composition
                                                                                                                                                          1. Sites of plaque formation; high turbulence and shear rates; clot = platelet rich (white clot)
                                                                                                                                                            1. Risk fators = smoking, high BP and cholesterol
                                                                                                                                                              1. Treatment = antiplatelet agents
                                                                                                                                                          2. Screens for thrombophilic patients
                                                                                                                                                            1. Screen for activated protein C resistence by clotting assay
                                                                                                                                                              1. activated partial thromboplastin time (aPTT)
                                                                                                                                                                1. Intrinsic pathway-based assay - coagulation activated by contact activator of XII
                                                                                                                                                              2. Genetic test for prothrombin mutation
                                                                                                                                                                1. Immunological assay for free and total protein S
                                                                                                                                                                  1. Measurement of fasting total plasma homocysteine
                                                                                                                                                                    1. ELISA assay
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