Circulation Disturbances Flashcards
Petechiae, Purpura, Hematoma, and Ecchymosis
Petechiae: Rash of pinpoint purplish red spots caused by intradermal or submucous hemorrhage 2 mm diameter
Hematoma: Collection of blood outside of a vessel
Ecchymosis: Bruise, Extravasation of intradermal hemorrhage, Subcutaneous hematoma
Exsanguination, Thrombus, Embolus, and Thrombophlebitis
Exsanguination: Severe loss of blood
Thrombus: Blood clot in a vessel
Embolus: Thrombus that has traveled and gets stuck
Thrombophlebitis: Inflammation of a vein (phlebitis) associated with thrombus formation
Blood vs. Vessel Abnormalities
Blood abnormalities: Humoral factors, platelets, qualitative versus quantitative
Vessel abnormalities: ie scurvy
Thrombosis
- Damaged vessel endothelium exposes subendothelial collagen and von Willebrand factor (VWF)
- Platelets adhere to these molecules, degranulate (release ADP) and recruit other platelets to adhere to the growing platelet plug, providing primary hemostasis
Coagulation cascade form fibrin = Thrombus
Partial Thromboplastin Time (aPTT)
Assesses the intrinsic and common pathways
Variable normal range
No international standard
Used to monitor heparin
Prothrombin Time (PT)
Assesses the extrinsic and common pathways
Normal about 10-12s
Reporting has been standardized as the international normal ratio (INR), ratio of value to range
Target for coumadin anticoagulant:
INR = 2-3 general, 2.5-3.5 for heart valves
Vitamin K Deficiency
Factors II, VII (shortest half life), IX, X
Protein C and Protein S
Vitamin K: Fat soluble, Leafy vegetables and colonic flora
Deficiency: Dietary (starvation), Fat malabsorption, Liver disease, Coumadin effect
These are vitamin K dependent factors… think about
Warfarin and how if it blocks vitamin K, then factors 2, 7, 9, 10, proteins S, and C are inhibited
Platelet Abnormalities
Quantitative: Thrombocytopenia
Skin and mucosal bleeding (Immediate postsurgical bleeding, petechiae, ecchymosis, epistaxis menorrhagia)
History of oozing flood loss with minor procedures, significant blood loss with menses, easily bruise
Spontaneous bleeding when 5000/uL
Qualitative: Decreased function ie connective tissue disorders, platelet granule dysfunction
Causes of Thrombocytopenia
Diminished production or release from bone marrow
Spurious: Platelet clumps in EDTA plasma, computerized platelet reader provides false results
Increased removal from circulation/decreased lifespan
Drugs: Idiopathic effect, chemotherapeutic effects
Toxins, chemical exposures
Viral illness: Transient
Marrow aplasia
Myelophthisis: Marrow replacement by metastatic cancer, fibrosis, or acute leukemia
Ineffective formation: Myelodysplasia
Splenic Sequestration: Look for splenomegaly => Physical exam
TTP (Thrombotic Thrombocytopenic Purpura)
Adults, 3rd decade, F>M, After virus
ADAMTS-13 {also problem in vWF2A} not degrading HMW vWF = large VWF multimers causes microthrombi and platelet consumption and microangiopathic hemolytic anemia
Pentad:Thrombocytopenia with purpura, Microangiopathic hemolytic anemia ie microthrombi shear circulating RBCs causing schistocytes, Fever, Neurologic changes, Renal dysfunction but less than HUS
HELLP Syndrome
Triad:
Microangiopathic hemolysis
Elevated liver enzymes
Low platelets
Obstetric disease assumed to be related to preeclampsia
ITP (Immune Thrombocytopenic Purpura)
*Antibody from spleen to platelet/platelet receptors
Platelets removed by spleen/liver without splenomegaly
Most common in young women
DIC (Disseminated Intravascular Coagulopathy)
Fibrinolytic syndrome, ie bleeders, and a consumptive coagulopathy
Clotting cascade is activated with formation of fibrin-platelet thrombi throughout the body, Fibrinolytic system also active simultaneously but not coordinated
Believed to be due to a problem with fibrinolytic system (plasmin)
Acute: Thrombocytopenia, Microangiopathic hemolytic anemia (fibrin strands causes schistocytes = RBC fragments on peripheral smear), Decreased fibrinogen and factor VIII
Elevated aPTT, PT, FSP including D dimer
Some causes: SEPSIS, shock, significant hemorrhage
Tx: transfusion of plasma and platelets
Coagulation Cascade Bleeding Problem
*Delayed and deep bleeding (deep muscle, joint, intracerebral or retroperitoneal bleeding), delayed postsurgical bleeding ie 1-4 hours
History is key, Personal and family
Ask questions about past surgeries, childbirth, trauma, bruising, medications and recent infections
Hemophilia A
*Factor VIII deficiency (Only factor from Kupffer cells in the liver and rest are from hepatocytes)
*Most common congenital coagulation factor deficiency {VWD is most common congenital bleeding disorder overall}
X linked (recessive) so see in males
Symptoms: Large hemorrhages into joint or body cavities, Post surgical bleeding delayed 1-4 hours, Easy bruising
Lab: aPTT elevated, Low plasma factor VIII activity
Hemophilia B
Factor IX deficiency (Vitamin K dependent)
X linked recessive so see in male but less common than hemophilia A
vWF
Protein subendothelially, on platelets and circulates as protein complex with Factor VIII (Factor VIII ie VIII:C and VWF aka VIII:R named for Factor VIII related protein)
Tests
vWF: Ag is quantity, (aka VIII:R)
Ristocetin cofactor =VWF activity
Factor VIII assay (Factor VIII:C): Factor VIII activity
Acts as a bridge between subendothelial collagen and platelets
Stabilizes Factor VIII in plasma and delivers Factor VIII to the platelet plug
Circulates as a multimer which is more effective for stabilizing Factor VIII
vWF Disease
Most common inherited coagulopathy, 1-2% of the US population
Multiple types describing quantitative and qualitative abnormalities in VWF, Most are autosomal dominant
Type 1 is most common subtype
Easy bruising, prolonged hemorrhage
Diagnosis: Prolonged PTT, Low plasma VWF Ag, Multimer analysis by electrophoresis
Treatment option: Desmopressin (DDAVP)
Fibrinolysis Cascade Summary
Plasmin (From plasminogen, Activator from endothelial cells, tPA activator and PAI inhibitor) breaks down fibrin get fibrin degradation products
***Plasminogen activator inhibitor 1 deficiency can cause excessive clot lysis and bleeding
Fibrin degradation products: FDG, FSP, fibrin split products, D dimmer degradation products of cross-linked fibrin,
Used diagnosis abnormal thrombotic states such as DIC, DVT, PE
Alpha2-antiplasmin inactivates plasmin, which then decreases fibrinolysis
Fibrinolysis Regulatory Mechanism
End product feedback
PAI-1 (plasminogen activator inhibitor 1):
Released from endothelial cells and inhibits tPA
Acute phase reactant
Chronic elevation related to increased risk of thrombosis
Alpha2-antiplasmin:
Inactivates plasmin to decrease fibrinolysis
Inherited deficiency is rare and causes bleeding
Arterial Thrombosis
Usually due to atheromatous plaque rupture ie Myocardial infarction/MI from thrombus in coronary artery
In heart or large arteries may get lines of Zahn ie layers of fibrin/platelets with intervening red cells
Virchow’s Triad
Categories of factors contributing to thrombosis
Changes in blood flow (hemostasis, turbulence): Ie heart failure, venous occlusion, or inactivity
Vessel wall changes (endothelial injury/dysfunction): Ie endothelial damage, vasculitis
Hypercoagulable state: Rare, Ie decreased anticoagulant factors or increased procoagulant factors (malignancy, oral contraceptives, increased concentrations of clotting factors
Activated Protein C (APC) Resistance
Base pair substitution error
***Produces factor V Leiden which is resistant to APC degradation, Oral contraceptives makes this worse
Lab: APC ratio
Prothrombin Gene mutation G20210A
Factor II elevation
causes excess prothrombin and therefore more thrombin, so susceptible to clots
Antithrombin III Deficiency
Thrombosis in unusual sites (mesenteric veins)
Review of Antithrombin 3/AT3: Anticlot, Synthesized in liver, Inhibits intrinsic pathway, Stimulated by Heparin
Protein C Deficiency
Protein C = anticoagulant
You have resistance from protein C to breakdown factor 5 in base pair substitution to alter the factor 5 (fV Leiden) and causes clot formation
Coumadin induced skin necrosis (exacerbation of hypercoagulable state via knocking out the rest of Protein C when loading coumadin)
Tx: heparin and proceed with warfarin slowly
Protein S Deficiency
Review of Protein S: Vitamin K dependent, helps bind APC
Antiphospholipid Syndrome
Thrombosis, recurrent fetal loss, possibly thrombocytopenia, possibly LLA (lupus like anticoagulants antibodies)
LLA: IgG toward phospholipid (PL in common pathway) but essential for aPTT reaction so prolongation of all aPTT tests, Can prolong PT based tests (DRVVT),
paradoxically causes thrombosis in patients
Associations: Autoimmune disorders like systemic lupus erythematosus
Trousseau’s Syndrome
Thrombosis associated with a visceral malignancy, especially adenocarcinoma of the pancreas
If you have a malignancy, the more likely you are to clot
