Heme part 2 Flashcards
Thrombosis
Occurs when balance is disturbed between:
Procoagulant factors
Anticoagulant factors
Procoagulant factors that get disturbed in thrombosis
Coagulation factors
Platelets
Leukocytes
Anticoagulant factors that get disturbed in thrombosis
Protein C
Protein S
Antithrombin
Thrombosis RFs
Age
Smoking
Obesity
Estrogen use
Types of thrombophilia
Inherited thrombophilic conditions
Acquired thrombophilic conditions
Factor V Leiden
The MC inherited thrombophilia
Point mutation (G1691A) in the factor V gene
Leads to an amino acid substitution that renders factor V resistant to inactivation by activated protein C (APC)
Dx of factor V Leiden
APC resistance assay
-Assess the ability of protein C to inactivate factor Va
PCR testing of the gene
Prothrombin G20210A
Gene mutation is the second most common inherited risk factor for VTE
Pts have slightly higher levels of circulating prothrombin (factor II)
Dx of prothrombin G20210A
PCR testing of the prothrombin gene
Obtaining factor II activity levels is NOT helpful
Pathophysiology of antithrombin deficiency
Antithrombin is an enzyme that interrupts the coagulation process, mainly by inhibitin thrombin and activated factors IX and X
Antithrombin deficiency types
Type I: quantitative
Type II: qualitative
Antithrombin deficiencies are typically _______
Heterozygous
Homozygous deficiencies are typically not compatible with life
Acquired cases of antihrombin deficiency that must be ruled out
Acute thrombosis Heparin therapy Liver dz Nephrotic dz Protein-loosing enteropathy
Labs for antithrombin deficiency
Genetic testing
Tx for antithrombin deficiency
Antithrombin concentrates may be used as adjunctive therapy with routine pharmacologic VTE prophylaxis or as a supplement when treateing VTE
Pathophysiology of Protein C deficiency
Protein C is a vit K-dependent natural anticoagulant
It is converted during the coagulation process to APC (which inactivates coagulation factors Va and VIIIa)
Types of protein C deficiency
Type I: quantitative
Type II: qualitative
Acquired conditions in protein C deficiency
Acute thrombosis
Warfarin therapy
Liver dz
Protein-losing enteropathy
Labs for protein C deficiency
Protein C activity assay
Genetic testing
What is protein C deficiency a risk factor for?
Primary VTE
Recurrent VTE
Arterial thromboembolism
When can protein C concentrate be given?
Indicated in infants with catastrophic thrombotic complications
Pathophys of Protein S deficiency
Natural vit K-dependent anticoagulant
Cofactor for APC
Labs for protein S deficiency
Protein S activity
Free protein S antigen
Acquired conditions in protein S deficiencies
Acute thrombosis Warfarin therapy Liver dz Inflammatory states Estrogens Protein-loosing enteropathy
What is protein S deficiency a RF for?
Primary VTE
Recurrent VTE
Arterial thromboembolism
Other inherited disorders
Dysfibrinogenemias- rare
Elevated homocysteine level
-Polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene
Elevated plasma factor VIII levels
RFs for acquired thrombotic conditions
Surgery Trauma Hospital or nursing home confinement/immobility Malignancy Central venous catheters Pacemaker placement Estrogen Pregnancy Obesity Inflammatory disorders Chemo Glucocorticoid therapy Smoking
Surgery, trauma, hospitalization and immobility in acquired thrombotic conditions
Higher risk with: Hip and knee arthroplasty CA surgery Pelvic surgery Abdominal surgery
40% of VTEs are associated with _________
Hospitalization
Either during or within 3 mos after d/c
CA and VTE
20% of all VTEs occur in pts with CA
Active CA increases VTE risk 5-6 fold
-Hx of CA, or CA that has undergone curative therapy without residual dz
6% of pts with unprovoked VTE have an undiagnosed CA at the time of the VTE
10% of pts with unprovoked VTE will be diagnosed with a CA in the year following the VTE dx
Antiphospholipid antibody syndrome
Acquired autoantibodies against phospholipids and phospholipid-binding proteins such as cardiolipin and B2-glycoprotein
Autoimmune, malignancy, drugs
Increases the risk of venous and arterial thrombosis
Labs for antiphospholipid antibody syndrome
Lupus anticoagulant Anticardiolipin antibodies -False pos syphilis test Anti-B2-GPI antibodies Presence of APLAs are found in nearly 505 of pts with SLE but only 1-5% of the general population
Tx of antiphospholipid antibody syndrome
Pts with APS and a hx of unprovoked VTE should received anticoag therapy for life
-Target INR range is 2-3
Catastophic APS is rare and results in multiorgan failure
-Tx includes: anticoagulation, high-dose glucocorticoids and other immunosuppressants, and plasma exchange
Meds in acquired thrombotic conditions
Estrogen-progestin contraceptives -Highest with progesting drospirenone Contraceptive patches and rings Hormone replacement therapy Chemo Tamoxifen Anastrozole Bevacizumba Erythropoiesis-stimulating agents
Hemodynamically stable pts and transfusions
Transfusion threshold hgb level of < 7 g/dL is recommended based on data
Transfusion strategies
Erythropoietin and darbepoetin are used to promote RBC production and reduce the need for transfusion
-Higher hemoglobins have increased risks
Preoperative autologous blood donation
-Reduces blood transfusion risks
Interoperative hemodilution or use of intraoperative cell salvage technology
FFP
Replacement solution for plasma exchange
Prevention of coagulopathy form massive transfusion
Tx of bleeding associated with multiple acquired clotting factor deficiencies (DIC)
Major warfarin-associated hemorrhage
Cryoprecipitate
Congenital or acquired fibrinogen deficiency
Dysfibrinogenemia
Factor XIII deficiency
Tx of hemophilia A and vWB dz when another more suitable product is not available
Immune globulin
Acquired or congenital hypogammaglobulinemia
Autoimmune disorders
Albumin
Replacement solution for plasma exchange
Spontaneous bacterial peritonitis
Prothrombin complex concentrates
Major warfarin-associated hemorrhage
Factor VIII
Hemophilia A
Tx and prevention of bleeding
Von Willebrand protein-rich factor VIII
Von Willebrand dz
Tx and prevention of bleeding
Factor IX
Hemophilia B
Tx and prevention of bleeding
Fibrinogen
Congenital fibrinogen deficiency
Tx of bleeding
Thrombin
Small vessel bleeding despite standard surgical techniques or when surgical intervention is not feasible (topical application)
Protein C concentrate
Severe congenital protein C deficiency
Prevention and tx of venous thrombosis and purpura fulminans
Antithrombin
Hereditary antithrombin deficiency
Alpha 1 antitrypsin
Congenital alpha 1 antitrypsin deficiency
C1-esterase inhibitor
Hereditary angioedema
Acute attacks
Conventional approaches to medical oncology
Histologic dx and clinical staging
Surgery, radiation therapy, chemo
New approaches to medical oncology
Molecular profiling
Targeted therapy, immunotherapy, use of immunoconjugates
What must be done before oncology pts can be treated?
Staging
Individualized clinical assessment
Mutually determine goals of therapy
T staging oncology- size or direct extent of the primary tumor
Tx: tumor cannot be assessed
Tis: carcinoma in situ
T0: no evidence of tumor
T1, T2, T3, T4: size and/or extension of the primary tumor
N staging oncology: degree of spread to regional lymph nodes
Nx: LNs cannot be assessed
N0: no regional lymph nodes metastasis
N1: regional lymph node metastasis present; at some sites, tumor spread to closest or small number of regional LNs
N2: tumor spread to an extent between N1 and N3
N3: tumor spread to more distant or numerous lymph nodes
M staging oncology- presence of distant metastasis
M0: no distant metastasis
M1: metastasis to distant organs (beyond regional lymph nodes)
Performance status in oncology
Indicates a pt’s well-being and ability to perform daily activities
-Karnofsky score
-Zubrod score
Pts with an excellent performance status typically have a better overall prognosis and the ability to tolerate more aggressive therapies
How is Karnofsky performance status scale scored?
100 is best, 0 is dead
How is the Zubrod scale scored?
O is nl activity, 4 is bedridden
MItotic rate
Measure of how fast CA cells are dividing and growing
Higher mitotic rates are linked with lower survival rates in oncology
Overall survival
Refers to the time from initiation of therapy until death
Frequently quoted as the median survival time
Progression-free survival (progression-free interval)
The time from initiation of therapy until the time therapy is not longer controlling the tumor growth
Overall response rate
The percentage of pts involved in a clinical trial whose tumor undergoes a prespecifed degree of shrinkage in imaging studies
Surgical resection
Primary tx for locoregional solid tumor malignancies
Adjuvant therapy
Chemo and/or radiation given after definitive surgery with curative intent
Neoadjuvant therapy
Chemo and/or radiation given before planned definitive surgery with curative intent
Traditional CA chemo
Cytotoxic agents with minimal selectivity for tumor cells over nl cells
Personalized targeted agents
Have more selective toxicity on tumor cells based on specific tumor biology
Tumor markers
Ovarian CA
Leading cause of GYN cancer-related deaths
Median age is 63 yrs
RF for ovarian CA
FHx (BRCA1/2 mutations)
PCOS
Endometriosis
Smoking
Decreased RF for ovarian cancer
Previous pregnancy
Prior OC
Tubal ligation or hysterectomy
Dx of ovarian CA
U/s
Bx
CA-125
Tx of ovarian CA
Surgery
+/- adjuvant chemo
Cervical CA
Mean age is 48 yrs
Invasive cervical CA incidence in the US by more than 80% since the 1940s owing to Pap smear screening
HPV subtypes 16 and 18
S/sx of cervical CA
Postcoital bleeding
Vaginal bleeding between menstrual cycles or after menopause
Colon Ca sx
Bright Red Blood Per Rectum
Melena
Chronic diarrhea or constipation
Cramping and bloating
Dx of colon CA
Colonoscopy
CEA
Tx of colon CA
Surgical resection
+/- adjuvant tx
5-fluorouracil
Rectal CA: details and tx
Adenocarcinoma
Tx: surgery +/- neoadjuvant chemoradiotherapy
Anal cancer
Epidermoid or squamous cell carcinoma
Typically associated with HPV
Tx of anal cancer
Often curable with radiation therapy and concurrent chemo with mitomycin plus 5-FU
Pancreatic CA
Surgical resection is the only potential curative intervention (CA 19-9)
Only 15-20% of cases are considered resectable at presentation
-Resectable tumors: IA, IB, IIA
-Borderline resectable- extends to nearby blood vessels but may be removed completely by surgery
-Unresectable
Gastroesophageal CA
Virtual all gastric and gastroesophageal junction CAs are adenocarcinomas, as are approximately 95% of esophageal CAs
Pts with adenocarcinomas and squamous cell carcinoma receive the same tx
Tx of gastroesophageal CA
Surgery
Chemoradiation
Non-small cell lung CA
80-90%
Adenocarcinoma is MC subtype
+/- paraneoplastic syndromes (hypercalcemia)
Tx: surgery, radiation, chemo
Small cell lung CA
Neuroendocrine tumor- smokers \+/- paraneoplastic syndromes (SIADH, hyponatremia) Limited-stage: 1 hemithorax Extensive-stage: beyond Tx: mostly chemo
