Clin Med/Pathophys Flashcards
hemophilia
A/B are congenital, X linked recessive deficiencies in coagulation factors VIII / IV. severe cases present in infant males w spontaneous bleeding, mild cases present with significant hemostatic events (surgery or trauma)
Deep Vein Thrombosis (DVT)
results from blood clot formation within large veins in the legs/pelvis.
thrombocytopenia
relative decrease in platelets in the blood with a platelet count <100,000 (normal is 150,000-300,000). characteristically produce petechial and purpuric lesions and bleeding from mucous surfaces
pulmonary embolism
blockage of the main artery of hoteling or one of its branches by a clot formation that has formed elsewhere and traveled through the bloodstream. most commonly results from DVT.
vit K deficiency etiology
deficient dietary intake, malabsorption, decreased production by intestinal bacteria, primary liver dz depletes stores
vit K deficiency pathophys
normally it k reductase assists in conversion of gamma-carboxyglutamic acid necessary for factors II, VII, IX, X. if deficient in bit k, clotting factor levels low, and will have prolonged PT
vit K deficiency s/sxs
bleeding
vit K deficiency mgmt
vit K PO or IV
vit K deficiency prognosis
improvement in PT in 1 day w PO; 8-10hrs w IV
disseminated intravascular coagulation (DIC) etiology
depletion of coagulation factor d/t bacterial sepsis, leukemia, lymphoma, or massive hemorrhage, burns, trauma, pregnancy, snake bites. concurrent uncontrolled generation of thrombin
disseminated intravascular coagulation (DIC) pathophys
widespread intravascular fibrin formation: systemic fibrin deposition in small and medium vessels. massive bleeding d/t platelet and clotting factor depletion. (the clots are blocking small vessels, and all the clotting factors are being used up in those vessels, and not where they are actually needed.)
disseminated intravascular coagulation (DIC) s/sxs
depends on magnitude of hemostasis imbalance: ranges from venipuncture oozing/ecchymosis/petechiae to uncontrolled bleeding throughout entire circulatory system. The clots can occlude blood flow to areas of body, as well.
disseminated intravascular coagulation (DIC) dx workup
increased PT & aPTT. thrombocytopenia. decreased fibrinogen levels. increase in fibrin degradation products. schistocytes on smear (fragmented RBCs)
disseminated intravascular coagulation (DIC) mgmt
treat underlying cause. in high risk pts, can transfuse platelets, cryoprecipitate (for fibrinogen), fresh frozen plasma and packed RBCs. Heparin for clots.
coagulopathy of liver disease etiology
cirrhosis or other hepatopathologies leading to impaired hepatic function. decreased synthesis of clotting factors II, VII, V, IX, and fibrinogen.
coagulopathy of liver disease pathophys
fewer clotting factors available = net decrease in clotting ability
coagulopathy of liver disease s/sxs
bleeding induced by any stressors. typically asymptomatic with incidentally finding on coagulation lab studies.
coagulopathy of liver disease mgmt
FFP infusion if active bleeding present. cryoprecipitate if bleeding + fibrinogen level low. liver transplant. recombinant human activated factor VII.
aplastic anemia etiology
bone marrow failure from suppression or injury to hematopoietic stem cells. inability to produce mature RBCs
aplastic anemia pathophys
most common cause is autoimmune suppression of hematopoiesis by a T cell mediated cellular mechanism “idiopathic” aplastic anemia. SLE can cause stem cell dysfunction through IgG autoantibody.
aplastic anemia s/sxs
anemia, fatigue/weakness, neutropenia leads to frequent infections, thrombocytopenia causes mucosal and skin bleeding
aplastic anemia dx workup
pancytopenia, anemia also associated with reticulocytopenia.
aplastic anemia mgmt
supportive care (erythropoietic and/or myeloid growth factors); severe cases may require BMT in meds, immunosuppression in adults.
aplastic anemia complications
infection, bleeding disorders, anemia, death
aplastic anemia prognosis
severe cases are rapidly fatal if left untreated
immune thrombocytopenic purpura (ITP) etiology
hemorrhagic syndrome with diverse causes that can occur in an acute or chronic form. characterized by reduction in # of circulating platelets, abundant megakaryoctytes in the bone marrow, and a shortened platelet life span. may be idiopathic or secondary to a lymphoproliferative disorder, drugs or toxins, bacterial or viral infection, SLE, or other conditions.
immune thrombocytopenic purpura (ITP)pathophys
circulating antiplatelet IgG autoantibody usually directed against a membrane protein, which is the fibrinogen receptor (glycoprotein IIb/IIIa). the spleen is primarily the site of platelet destruction and may also be a significant source of autoantibody production.
immune thrombocytopenic purpura (ITP) s/sxs
acute onset: ecchymosis or showers of petechiae, may have bleeding gums, vaginal bleeding, GI bleeding, hematuria. chronic: insidious onset, often w long hx of bruising easily and menorrhagia. showers of petechiae may occur
immune thrombocytopenic purpura (ITP) dx workup
labs: platelet count is mod to severely decreased. WBC & RBC usually normal although iron deficiency anemia may be present as a result of bleeding. bone marrow shows increased # of large megakaryocytes without platelet budding. bleeding time is prolonged. capillary fragility greatly increased. poor clot retraction. PTT/PT, and coat time are normal.
immune thrombocytopenic purpura (ITP) mgmt
depends on age of pt, severity of dz, duration of thrombocytopneia, and clinical variant. secondary immune thrombocytopenia are best managed by tx the underlying primary disorder. pts with mild or no sxs don’t nd tx but should avoid contact sports, elective surgeries, and unessential meds. corticosteroids can be used in pts with mod to severe purpura of short duration
thrombotic thrombocytopenic purport (TTP) etiology
ADAMTS13 is reduced in amount or function, allowing persistence of many unusually LARGE vWF multimers; identification of these multimers is diagnostic for TTP.
thrombotic thrombocytopenic purport (TTP) pathophys
association with ADAMTS-13 (von Willebrand factor [vWF]-cleaving protease) deficiency.
oversized vWF results in platelet over activation leading to thrombus formation.
microthrombi of agglutinated platelets form in microvasculature, occluding arterioles and capillaries.
tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-gamma act in synergy to induce apoptosis in microvascular endothelial cells, but spare large vessels and pulmonary vessels
thrombotic thrombocytopenic purport (TTP) s/sxs
classic pentad of TTP = microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal failure, fever. Usually systemic, but can be localized. most common symptoms include: weakness, anorexia, vomiting, diarrhea, nausea. neurological symptoms: generalized headache, seizures, confusion, coma, transient ischemic attack (TIAs)
thrombotic thrombocytopenic purport (TTP) dx workup
The hemolytic anemia is characterized by many circulating fragmented erythrocytes in the form of schistocytes and helmet cells. High lactate dehydrogenase (LDH) levels correlate with the severity of the disease. Renal manifestations include microscopic hematuria, rarely gross hematuria, mild to moderate proteinuria, and azotemia with up to 10% of patients having acute renal failure. Renal biopsy may show thrombi with a higher number of platelets and fewer erythrocytes or fibrin.
thrombotic thrombocytopenic purport (TTP) mgmt
Corticosteroids + plasma exchange Low-dose aspirin when platelets recover Folate supplements Refractory cases consider: Ritixumab, Cyclophosphamide, Cyclosporine Splenectomy (severe cases) Red Cell Transfusion
Hemolytic uremic syndrome (HUS) etiology
acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. It is seen mostly in children and most cases are preceded by hemorrhagic diarrhea (E. Coli is the most common cause). Can present without preceding diarrhea (called DHUS) which is caused by dysregulation of the complement system.
Hemolytic uremic syndrome (HUS) pathophys
Infection induced by GI illness with diarrhea (EHEC most common cause), has also been associated with invasive pneumococcal disease, or less commonly due to genetic abnormalities affecting the complement pathway. Damage may occur to the endothelial cells, mesangial cells, renal tubular epithelial cells, or monocytes. Proinflammatory and prothrombotic changes in the coagulation pathway may damage the endothelial cells and lead to organ damage.
Hemolytic uremic syndrome (HUS) s/sxs
Prodromal GI illness with diarrhea, often bloody; symptoms of anemia; neuro symptoms (irritability, lethargy, confusion, stroke, seizures); possible jaundice from hemolysis
Hemolytic uremic syndrome (HUS) dx workup
Hemolytic anemia – hct <30% with evidence of erythrocyte destruction on peripheral blood smear. Low platelet count. High serum creatinine.
Hemolytic uremic syndrome (HUS) mgmt
Control of fluid/electrolyte imbalance; RBC transfusion for cardiovascular or respiratory compromise; control of hypertension; dialysis if acute renal failure unresponsive to fluid mgmt; nutritional support; avoid antimotility agents
Hemolytic uremic syndrome (HUS) complications
Acute renal failure, chronic kidney dz, possible neurologic complications (seizures), acute heart failure, GI perforation or intestinal strictures.
Henoch-Schonlein purpura etiology
Common systemic vasculitis. More commonly in children. Nonthrombocytopenic purpura caused by inflammation in the blood vessels of the superficial dermis. The dz usually occurs about 10 days after the start of a URI, but no single microorganism or environmental factor has been confirmed as the cause.
Henoch-Schonlein purpura pathophys
Leukocytoclastic vasculitis and deposition of IgA in the walls of involved blood vessels (typically small vessels). This is a form of vasculitis characterized by IgA dominant immune deposits in the vessel walls, small-vessel involvement (capillaries, venules, arterioles), with skin/gut/renal/and joint manifestations.
Henoch-Schonlein purpura s/sxs
Acute onset fever, palpable purpura on lower extremities (but can also be seen on hands/arms/trunk/buttocks), abdominal pain (typically colicky and worse after eating, the result of edema of the bowel wall & hemorrhage induced by mesenteric vasculitis), arthritis (most commonly the knees and ankles), hematuria (signals the presence of a glomerular lesion that is usually reversible, although it occasionally may progress to chronic kidney dz).
Henoch-Schonlein purpura dx workup
Skin biopsy can demonstrate leukocytoclastic vasculitis with IgA deposition. Kidney biopsy shows segmental glomerulonephritis with crescents and mesangial deposition of IgA. Diagnosis should be confirmed by biopsy.
Henoch-Schonlein purpura mgmt
NSAIDS may alleviate arthralgias, but can aggravate GI symptoms and should be avoided in pts with renal dz. Dapsone (100mg/day) may be effective, maybe through interference with the interactions of IgA and neutrophils, but not really known. Glucocorticoids may help with the joint/GI symptoms, but not with the rash or the renal dz.
Henoch-Schonlein purpura prognosis
The dz is self-limited most of the time, resolving within a few weeks.
Heparin induced thrombocytopenia etiology
Thrombocytopenia within 5-10 days of exposure to heparin. Decline in baseline platelet count of 50% or greater. Affects about 3% of pts who are exposed to unfractionated heparin and .6% of pts who are exposed to low-molecular wt heparin
Heparin induced thrombocytopenia pathophys
Results from the formation of IgG antibodies to heparin-platelet factor 4 complexes. The antibodies then bind platelets, which activates them. This platelet activation leads to both thrombocytopenia and a pro-thrombotic state.
Heparin induced thrombocytopenia s/sxs
Usually asymptomatic. Bleeding does not usually occur.
Heparin induced thrombocytopenia mgmt
Immediate discontinuation of the heparin. Platelet transfusions are rarely necessary. Direct Thrombin Inhibitor: Argatroban administered immediately and should be continued until the platelet count has recovered to at least 100,000/mcL, at which point treatment with a vitamin K agonist (Warfarin) should be initiated.
Factor VIII deficiency (Hemophilia A) etiology
X-linked recessive genetic disorder of clotting factor VIII
Factor VIII deficiency (Hemophilia A) pathophys
Genetic
Factor VIII needs to be activated in the intrinsic pathway, so that factor X can be cleaved & eventually lead to a fibrin crosslinked clot.
Bleeding results from altered clot formation
Factor VIII deficiency (Hemophilia A) s/sxs
excessive bleeding w/ or w/o trauma: bleeding into joints, epistaxis.
hemorrhage disproportionate to trauma.
spontaneous hemorrhage (joints, muscles, CNS, GI, & GU all common locations).
family h/o bleeding.
Factor VIII deficiency (Hemophilia A) d/dx
- -CALF DIPS mnemonic: Cirrhosis/ liver dz, Asa& other NSAIDs, Leukemia, Factor VIII or IX dysfunction, Disseminated intravascular coagulation, Ideopathic thrombocytopenic purpura, Platelet deficiency, Scurvy
- -if pt. reports weight loss also: cancer, HIV, RA, SLE, thyroid dz, renal dz
- -vWD, deficiency of other clotting factors, other hemophilias
Factor VIII deficiency (Hemophilia A) mgmt
factor VIII,Prompt, aggressive management of hemorrhages, Antihemolytic agents (desmopressin), monoclonal Abs (rituximab)
Factor VIII deficiency (Hemophilia A) dx workup
CBC: normal to low Hg & platelet count; Factor VIII assay; coagulation study: normal to severely prolonged aPTT w/ a normal PT & bleeding time; Can do genetic testing
Von Willibrand Dz (vWF) etiology
Autosomal dominant genetic mutation in VWF gene resulting in a quantitative or qualitative defect in vWF; most frequent bleeding disorder (1% prevalence), affects males & females; poor platelet adhesion to vascular walls and deficient factor VIII availability
Von Willibrand Dz (vWF) pathophys
vWF is made & stored in endothelial cells & platelets. vWF allows platelets to resist the force of blood flow & adhere to exposed collagen of damaged vessel walls. vWF is also a carrier protein for clotting factor VIII.
→ vWF defect prevents proper platelet plug formation and stalls clotting cascade @ factor VIII
Von Willibrand Dz (vWF) s/sxs
excessive bleeding (easy bruising, bleeding gums, epistaxis, menorrhagia). bleeding into joint is rare.
Von Willibrand Dz (vWF) dx workup
Prolonged bleeding time, low vWF, low factor VIII procoagulant levels, decreased platelet aggregation when ristocetin is added to plasma
Von Willibrand Dz (vWF) mgmt
varies depending on type/ subtype involved; Tx & prevent bleeding complications: desmopressin acetate, cryoprecipitate fresh, frozen plasma, factor VIII concentrate
Factor IX deficiency (Hemophilia B) etiology
X-linked recessive genetic disorder (point mutations & deletions of F9 gene on long arm of X chromosome; generally inherited, but spontaneous mutation & mut. after infection have been seen)
Factor IX deficiency (Hemophilia B) pathophys
Deficiency of functional factor IX= insufficient thrombin produced by intrinsic pathway, so only platelet plug forms. Lack of crosslinked fibrin clot enables easy bleeding
Factor IX deficiency (Hemophilia B) s/sxs
excessive bleeding w/ or w/o trauma: bleeding into joints, epistaxis.
hemorrhage disproportionate to trauma.
spontaneous hemorrhage (joints, muscles, CNS, GI, & GU all common locations).
family h/o bleeding.
Factor IX deficiency (Hemophilia B) dx workup
CBC: normal to low Hg & platelet count; Factor IX assay; coagulation study: normal to severely prolonged aPTT w/ a normal PT & bleeding time; Can do genetic testing
Factor IX deficiency (Hemophilia B) mgmt
factor IX,Prompt, aggressive management of hemorrhages, Antihemolytic agents (desmopressin), monoclonal Abs (rituximab)
