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Flashcards in Heme part 2 Deck (86):
1

Thrombosis

Occurs when balance is disturbed between:
Procoagulant factors
Anticoagulant factors

2

Procoagulant factors that get disturbed in thrombosis

Coagulation factors
Platelets
Leukocytes

3

Anticoagulant factors that get disturbed in thrombosis

Protein C
Protein S
Antithrombin

4

Thrombosis RFs

Age
Smoking
Obesity
Estrogen use

5

Types of thrombophilia

Inherited thrombophilic conditions
Acquired thrombophilic conditions

6

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)

7

Dx of factor V Leiden

APC resistance assay
-Assess the ability of protein C to inactivate factor Va
PCR testing of the gene

8

Prothrombin G20210A

Gene mutation is the second most common inherited risk factor for VTE
Pts have slightly higher levels of circulating prothrombin (factor II)

9

Dx of prothrombin G20210A

PCR testing of the prothrombin gene
Obtaining factor II activity levels is NOT helpful

10

Pathophysiology of antithrombin deficiency

Antithrombin is an enzyme that interrupts the coagulation process, mainly by inhibitin thrombin and activated factors IX and X

11

Antithrombin deficiency types

Type I: quantitative
Type II: qualitative

12

Antithrombin deficiencies are typically _______

Heterozygous
Homozygous deficiencies are typically not compatible with life

13

Acquired cases of antihrombin deficiency that must be ruled out

Acute thrombosis
Heparin therapy
Liver dz
Nephrotic dz
Protein-loosing enteropathy

14

Labs for antithrombin deficiency

Genetic testing

15

Tx for antithrombin deficiency

Antithrombin concentrates may be used as adjunctive therapy with routine pharmacologic VTE prophylaxis or as a supplement when treateing VTE

16

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)

17

Types of protein C deficiency

Type I: quantitative
Type II: qualitative

18

Acquired conditions in protein C deficiency

Acute thrombosis
Warfarin therapy
Liver dz
Protein-losing enteropathy

19

Labs for protein C deficiency

Protein C activity assay
Genetic testing

20

What is protein C deficiency a risk factor for?

Primary VTE
Recurrent VTE
Arterial thromboembolism

21

When can protein C concentrate be given?

Indicated in infants with catastrophic thrombotic complications

22

Pathophys of Protein S deficiency

Natural vit K-dependent anticoagulant
Cofactor for APC

23

Labs for protein S deficiency

Protein S activity
Free protein S antigen

24

Acquired conditions in protein S deficiencies

Acute thrombosis
Warfarin therapy
Liver dz
Inflammatory states
Estrogens
Protein-loosing enteropathy

25

What is protein S deficiency a RF for?

Primary VTE
Recurrent VTE
Arterial thromboembolism

26

Other inherited disorders

Dysfibrinogenemias- rare
Elevated homocysteine level
-Polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene
Elevated plasma factor VIII levels

27

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

28

Surgery, trauma, hospitalization and immobility in acquired thrombotic conditions

Higher risk with:
Hip and knee arthroplasty
CA surgery
Pelvic surgery
Abdominal surgery

29

40% of VTEs are associated with _________

Hospitalization
Either during or within 3 mos after d/c

30

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

31

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

32

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

33

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

34

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

35

Hemodynamically stable pts and transfusions

Transfusion threshold hgb level of < 7 g/dL is recommended based on data

36

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

37

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

38

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

39

Immune globulin

Acquired or congenital hypogammaglobulinemia
Autoimmune disorders

40

Albumin

Replacement solution for plasma exchange
Spontaneous bacterial peritonitis

41

Prothrombin complex concentrates

Major warfarin-associated hemorrhage

42

Factor VIII

Hemophilia A
Tx and prevention of bleeding

43

Von Willebrand protein-rich factor VIII

Von Willebrand dz
Tx and prevention of bleeding

44

Factor IX

Hemophilia B
Tx and prevention of bleeding

45

Fibrinogen

Congenital fibrinogen deficiency
Tx of bleeding

46

Thrombin

Small vessel bleeding despite standard surgical techniques or when surgical intervention is not feasible (topical application)

47

Protein C concentrate

Severe congenital protein C deficiency
Prevention and tx of venous thrombosis and purpura fulminans

48

Antithrombin

Hereditary antithrombin deficiency

49

Alpha 1 antitrypsin

Congenital alpha 1 antitrypsin deficiency

50

C1-esterase inhibitor

Hereditary angioedema
Acute attacks

51

Conventional approaches to medical oncology

Histologic dx and clinical staging
Surgery, radiation therapy, chemo

52

New approaches to medical oncology

Molecular profiling
Targeted therapy, immunotherapy, use of immunoconjugates

53

What must be done before oncology pts can be treated?

Staging
Individualized clinical assessment
Mutually determine goals of therapy

54

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

55

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

56

M staging oncology- presence of distant metastasis

M0: no distant metastasis
M1: metastasis to distant organs (beyond regional lymph nodes)

57

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

58

How is Karnofsky performance status scale scored?

100 is best, 0 is dead

59

How is the Zubrod scale scored?

O is nl activity, 4 is bedridden

60

MItotic rate

Measure of how fast CA cells are dividing and growing
Higher mitotic rates are linked with lower survival rates in oncology

61

Overall survival

Refers to the time from initiation of therapy until death
Frequently quoted as the median survival time

62

Progression-free survival (progression-free interval)

The time from initiation of therapy until the time therapy is not longer controlling the tumor growth

63

Overall response rate

The percentage of pts involved in a clinical trial whose tumor undergoes a prespecifed degree of shrinkage in imaging studies

64

Surgical resection

Primary tx for locoregional solid tumor malignancies

65

Adjuvant therapy

Chemo and/or radiation given after definitive surgery with curative intent

66

Neoadjuvant therapy

Chemo and/or radiation given before planned definitive surgery with curative intent

67

Traditional CA chemo

Cytotoxic agents with minimal selectivity for tumor cells over nl cells

68

Personalized targeted agents

Have more selective toxicity on tumor cells based on specific tumor biology
Tumor markers

69

Ovarian CA

Leading cause of GYN cancer-related deaths
Median age is 63 yrs

70

RF for ovarian CA

FHx (BRCA1/2 mutations)
PCOS
Endometriosis
Smoking

71

Decreased RF for ovarian cancer

Previous pregnancy
Prior OC
Tubal ligation or hysterectomy

72

Dx of ovarian CA

U/s
Bx
CA-125

73

Tx of ovarian CA

Surgery
+/- adjuvant chemo

74

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

75

S/sx of cervical CA

Postcoital bleeding
Vaginal bleeding between menstrual cycles or after menopause

76

Colon Ca sx

Bright Red Blood Per Rectum
Melena
Chronic diarrhea or constipation
Cramping and bloating

77

Dx of colon CA

Colonoscopy
CEA

78

Tx of colon CA

Surgical resection
+/- adjuvant tx
5-fluorouracil

79

Rectal CA: details and tx

Adenocarcinoma
Tx: surgery +/- neoadjuvant chemoradiotherapy

80

Anal cancer

Epidermoid or squamous cell carcinoma
Typically associated with HPV

81

Tx of anal cancer

Often curable with radiation therapy and concurrent chemo with mitomycin plus 5-FU

82

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

83

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

84

Tx of gastroesophageal CA

Surgery
Chemoradiation

85

Non-small cell lung CA

80-90%
Adenocarcinoma is MC subtype
+/- paraneoplastic syndromes (hypercalcemia)
Tx: surgery, radiation, chemo

86

Small cell lung CA

Neuroendocrine tumor- smokers
+/- paraneoplastic syndromes (SIADH, hyponatremia)
Limited-stage: 1 hemithorax
Extensive-stage: beyond
Tx: mostly chemo