7. Clinical Considerations (Hematology) Pt. I

Question 1

Congenital Bleeding Disorders
Introduction

• Hereditary bleeding disorders are a diverse group of diseases that include abnormalities of primary and secondary hemostasis.
• Primary hemostasis involves formation of the ____ which involves ____, the blood vessel wall and ____; abnormalities can include problems in platelet ____, adhesion or aggregation.
• Secondary hemostasis involves the formation of ____ through the coagulation cascade; abnormalities include deficiencies of ____ factors, deficiencies or abnormalities of ____ or connective tissue diseases

Answer 1

platelet plug
platelets
von willebrand factor
number

fibrin
coagulation
fibrinogen

Question 2

Congenital Bleeding Disorders
Introduction
• The most common congenital bleeding disorders include: 
-\_\_\_\_ disease
-Hemophilia A (factor \_\_\_\_ deficiency)
-Hemophilia B (factor \_\_\_\_ deficiency)

Answer 2

von willebrand
VIII
IX

Question 3

Congenital Bleeding Disorders
Laboratory Evaluation
• When tissue is injured it initiates the ____ cascade leading to the formation of a blood clot.

• This cascade is comprised of three pathways: extrinsic, intrinsic, and common.
• Two laboratory tests are used commonly to evaluate coagulation disorders: Prothrombin Time (PT) which measures the integrity of the ____ system as well as factors common to both systems and Partial Thromboplastin Time (PTT), which measures the integrity of the ____ system and the common components.

Answer 3

coagulation
extrinsic
intrinsic

Question 4

Congenital Bleeding Disorders
Laboratory Evaluation - PT
• The PT test is used to monitor patients taking certain medications as well as to help diagnose clotting disorders.
• The PT test is performed by adding the patient’s plasma to some source of ____ and calcium chloride. The test is timed from the addition of the calcium chloride until the plasma ____. This time is called the Prothrombin Time.
• The prothrombin test specifically evaluates the presence of factors I (____), II (____), ____, ____, and ____.

Answer 4

tissue factor
clots

fibrinogen
prothrombin
V
VII
X

Question 5

Congenital Bleeding Disorders
Laboratory Evaluation - PT
• A ____ PT indicates a deficiency in any of factors: I (fibrinogen), II (prothrombin), V, VII, and X.

• Vitamin K deficiency: Vitamin K is needed for synthesis of factors II (____), ____, ____ and ____.
• Liver disease: The liver hepatocytes synthesize all clotting factors except ____ which is synthesized by the liver ____ endothelial cells
• Medications: Coumadin (____) inhibits the vitamin K dependent clotting factors, mimicking vitamin K deficiency.

Answer 5

prologned

prothrombin
VII
IX
X

VIII
sinusoidal
warfarin

Question 6

Congenital Bleeding Disorders

Laboratory Evaluation - PT
• The PT was introduced in 1935,it was originally used to detect a coagulation disorder in chickens but was later adapted for control of oral anticoagulants.
• Universal adoption of the PT test unfortunately did not produce uniform or safe oral anticoagulant dosage because of the failure to ____ the thromboplastin in the PT and also because of different methods of reporting results.
• The ____ was introduced in an attempt to standardize the PT.

Answer 6

standardize

INR

Question 7

Congenital Bleeding Disorders
Laboratory Evaluation - PTT

• The activated partial thromboplastin time (aPTT) test is used to monitor patients taking certain medications as well as to help ____ clotting disorders.
• The aPTT test is performed by adding ____ and ‘activating substances’ to the patients plasma. This starts the ____ pathway of the coagulation cascade. The partial thromboplastin time is the time it takes for a ____ to form.

Answer 7

diagnose
calcium
intrinsic
clot

Question 8

Congenital Bleeding Disorders
Laboratory Evaluation - PTT
• A prolonged PTT indicates a deficiency in any of factors: ____, ____, ____, ____ and ____ clotting pathways.
• Liver disease: The liver hepatocytes synthesize all clotting factors except ____ which is synthesized by the liver sinusoidal endothelial cells
• Medications: ____ inhibits the blood coagulation by binding to antithrombin III which functions as a inactivator of active clotting factors as factors ____.

Answer 8

VIII
IX
XI
XII

VIII
V, IX, X, XI and XII

Question 9

Congenital Bleeding Disorders
Laboratory Evaluation – Summary
• PT (INR): Evaluates the ____ and common pathway. Used to monitor Coumadin (____).
• PTT: Evaluates the ____ and common pathway. Used to monitor ____.

Answer 9

extrinsic
warfarin
intrinsic
heparin

Question 10

Congenital Bleeding Disorders

Risk assessment
• The four methods by which you can identify a patient who may have a bleeding disorder are a good ____, careful physical ____, screening ____ tests, and occurrence of excessive ____ after a dental procedure.
• A history of spontaneous ____ and muscle hemorrhages is suggestive of severe hemophilia.
• A history of frequent ____, gingival bleeding, and ____ are found in patients with thrombocytopenia, platelet disorders, or von Willebrand disease.

Answer 10

history
examination
laboratory
bleeding

hemarthroses
epistaxis
menorrhagia

Question 11

Congenital Bleeding Disorders

Risk assessment
• Inspect the exposed skin and mucosa of the oral cavity and pharynx for signs that might indicate a possible bleeding disorder.
• Signs include ____, ecchymoses, spider ____, telangiectasias, ____, pallor, and cyanosis.
• When any of these signs are found that cannot be explained by the history or other clinical findings, the patient should be referred for ____ evaluation prior to invasive treatment.

Answer 11

petechiae
angioma
jaundice
medical

Question 12

Congenital Bleeding Disorders

Von Willebrand Disease
• Von Willebrand disease is an inherited disease marked by ____ deficiency.
• It is the most common ____ bleeding disorder, affecting 1% of the population and affects both ____ equally.
• vWF acts as a carrier for factor ____ and increases its half- life and is important for platelet ____ at wound sites.

Answer 12

von willebrand factor (vWF)
congenital
sexes
VIII
adhesion

Question 13

Congenital Bleeding Disorders
Von Willebrand Disease • There are 3 types:
• Type 1: ____ defect. Generally have vWF levels ____% of normal. Most common, ____ severe.
• Type 2: ____ defect. ____ vWF levels, but they are ____.
• Type 3: Almost complete ____ of vWF. Most ____ form of disease.

Answer 13

quantitative
20-50
least

qualitative
normal
defective

absence
severe

Question 14

Congenital Bleeding Disorders

Von Willebrand Disease
• Screening tests show a ____ platelet count and, possibly, a slightly ____ PTT.
• Diagnosis is based on low levels of ____ antigen and abnormal ____ activity.

Answer 14

normal
prolonged
vWF
ristocetin cofactor

Question 15

Congenital Bleeding Disorders

Von Willebrand Disease
• Mild variants are characterized by a history of cutaneous and mucosal ____. In the more severe forms of the disease, ____ and dissecting intramuscular hematomas may occur.
• ____ are rare in these patients. However, GI bleeding, epistaxis, and menorrhagia are very common.
• Serious bleeding can occur in these patients after ____ or surgical procedures.

Answer 15

bleeding
hemarthoses
petechiae
trauma

Question 16

Congenital Bleeding Disorders
Von Willebrand Disease
• Management of these patients depend on the type of procedure and the type of Von Willebrand disease the patient is diagnosed with.
• Available treatment options include ____, factor VIII concentrates with vWF multimers (Humate-P), and ____ (DDAVP).

Answer 16

cryoprecipitate

desmopressin

Question 17

Congenital Bleeding Disorders
Von Willebrand Disease
• Desmopressin is an analog of ____ (vasopressin) that stimulates the release of ____ into the plasma causing a 2 to 5-fold increase in plasma von Willebrand factor and factor ____ concentrations.
• Desmopressin may be helpful for type ____ VWD but is usually of no value in other types.

Answer 17

ADH
vWF
VIII
1

Question 18

Congenital Bleeding Disorders
Von Willebrand Disease
• Patients with type 2 and 3 Von Willebrand disease are treated with factor ____ replacement that contains____ (Humate-P).

Answer 18

VIII

vWF multimers

Question 19

Congenital Bleeding Disorders

on Willebrand Disease
• ____ agents are used in conjunction with clotting factor replacement therapy.
• These agents include ____ analogs such as ____ and aminocaproic acid (Amicar). Both agents can be taken ____ or intravenously.
• These drugs prevent postoperative bleeding by inhibiting the activation of ____ to plasmin, which works to degrade fibrin clots.

Answer 19

antifibrinolytic
lysine
tranexamic acid
orally
plasminogen

Question 20

Congenital Bleeding Disorders

Hemophilia
• Hemophilia is an ____ disorder caused by a deficiency in blood coagulation factors. It is the second most common coagulation disorder after von Willebrand disease.
• Hemophilia A is characterized by a deficiency of factor ____
• Hemophilia B is caused by a deficiency of factor ____.
• The incidence is estimated to be 1 in ____ males for hemophilia A and 1 in ____ males for hemophilia B.

Answer 20

x-linked recessive
VIII
IX
5,000
30,000

Question 21

Congenital Bleeding Disorders
Hemophilia

• The first manifestation of hemophilia may be bleeding from the ____ when deciduous tooth exfoliates or prolonged bleeding following dental hygiene procedures or tooth extractions.
• The incidence of dental caries and periodontal disease is ____ in patients with bleeding disorders, which may be related to lack of effective oral ____ due to fear of bleeding.
• The importance of good oral ____ should be stressed reduce the chances of future problems.

Answer 21

gingiva
higher
hygiene
hygiene

Question 22

Congenital Bleeding Disorders
Hemophilia

• The management of patients with requires collaboration with the patient’s hematologist
as well as an awareness of local hemostatic measures and techniques that cause the least amount of trauma.
• Routine dental procedures can cause soft tissue ____ as well as local ____.
• Fatal hemorrhage in hemophiliac patients has been reported following local anesthetic injections due to ____.

Answer 22

trauma
bleeding
airway compromise

Question 23

Congenital Bleeding Disorders

Hemophilia
• To prevent complications, discuss treatment with their hematologist. Explain the procedure, expected bleeding and the types of postoperative local hemostatic measures that will be applied.

• Various types of medical interventions can be selected by the hematologist to increase the level of factor based on the patients deficiency and severity of the dental procedures. Agents that can be administered include ____, factor concentrate, ____ factors, and antifibrinolytic agent (____ or amicar).

Answer 23

desmopressin acetate
recombinant
tranexamic acid

Question 24

There are different severities for hemophilia.

Mild factor VIII deficiency - will get ____ care, can do most dentistry, except very ____ procedure you will want to consult hematologist.

Moderate to severe - you want to coordinate with ____ prior to much of anything. Some of the discussion will be about how much factor needs to be replaced in order to perform a specific procedure (more ____ therapy needed for extraction than for a prophy).

Answer 24

preventative
invasive

hematologist
replacement

Question 25

Congenital Bleeding Disorders

Hemophilia
• If local anesthesia is necessary, there is an 80% chance that a patient with hemophilia will develop a ____ following the administration of an ____ nerve block injection without prior factor infusion.
• Consider mandibular ____ infiltration with 4% ____ which has better efficacy compared to 2% Lidocaine.

Answer 25

hematoma
inferior alveolar
buccal
articaine

Question 26

Congenital Hypercoagulable Disorders
Introduction
• Primary hypercoagulable states result from a deficiency of ____ factors or increased ____ factors.
• Usually diagnosed in early adulthood with the development of a ____ or ____.

Answer 26

antithrombotic
prothrombotic
deep vein thrombosis
thromboembolism

Question 27

Congenital Hypercoagulable Disorders

Protein C deficiency
• Protein C deficiency leads to unregulated ____ generation because of impaired ____ of factors ____, two essential cofactors in the coagulation cascade.
• The prevalence of ____ protein C deficiency in the general population is about 1 per 200 to 500.

Answer 27

fibrin
inactivation
VIIIa and Va
heterozygous

Question 28

Congenital Hypercoagulable Disorders

Protein S deficiency
• Protein S is the principal cofactor of activated ____, and its deficiency mimics that of ____ deficiency.
• Impaired inactivation of factors ____ and ____ create a loss of regulation of fibrin generation.

Answer 28

protein C
protein C
VIIIa
V

Question 29

Congenital Hypercoagulable Disorders

Factor V Leiden
• Factor V Leiden is a mutated form of factor V in which protein C is not able to bind, leading to a ____ state.
• The factor V Leiden mutation (activated ____ resistance) is occurs in about 5% of the ____ population but is less prevalent in African andAsian populations.

Answer 29

hypercoagulable
protein C
caucasian

Question 30

Congenital Hypercoagulable Disorders

Dental management
• Generally speaking, hypercoagulable patients do not need any ____ in their routine dental care.
• Some of these patients will be on oral anticoagulants to prevent thromboembolism. This can be for 6 months after an ‘event’ or possibly ____.
– Discuss timing for invasive treatment with ____.
• If a patient had a stroke or TIA, deferral of treatment is advised for ____ months because the risk for another stroke remains high during this period.

Answer 30

alteration
lifelong
hematologist
6

Question 31

Disorders of RBC

Anemia
• Anemia is defined as a reduction in the ____ of the blood. It is usually associated with a decreased number of circulating ____ or an abnormality in ____. Anemia is generally defined as Hb level less than ____ g/dL for women and less than ____ g/dL for men.
• Causes:
-Decreased production of RBCs (____ deficiency, folate deficiency, pernicious anemia)
-Increased rate of destruction of circulating RBCs (____, autoimmune destruction).
-____ loss

Answer 31

oxygen carrying capacity
RBCs
hemoglobin
12
13

iron
hypersplenism
blood

Question 32

Disorders of RBC

Anemia
• Anemia increases the risk for ____, chronic kidney disease and death.
• Pernicious anemia is associated with increased risk of ____.
• Sickle cell anemia is associated with increased risk of ____, infection, osteonecrosis of the hip and shoulder joints, ____ disease, hypertension, and sudden death from ____.
• Aplastic anemia is associated with ____ issues, infection, and death.

Answer 32

acute myocardial infarction
gastric carcinoma
stroke
liver
bleeding

Question 33

Disorders of Red Blood Cells

Anemia – Laboratory evaluation
• Hemoglobin: Grams of ____ per 100 mL of whole blood (g/dL).
• Hematocrit: The packed spun volume of blood that consists of intact ____, expressed as a ____.
• RBC count: The number of RBCs contained in a specified volume of whole blood.
• In patients with anemia, hemoglobin and hematocrit typically ____ in parallel.
• RBC count also parallels them except in cases of extreme microcytosis such as ____, in which the RBC count may be ____ despite the presence of anemia.

Answer 33

hemoglobin
RBCs
percentage
decrease
thalassemia
increased

Question 34

Disorders of Red Blood Cells

Anemia – Laboratory evaluation
• Mean corpuscular volume (MCV): The average ____ (size) of the patient’s RBCs.
• Mean corpuscular hemoglobin (MCH): The average hemoglobin ____ in a RBC.
• Mean corpuscular hemoglobin concentration (MCHC): The average hemoglobin ____ per RBC.
• Red cell distribution width (RDW): A measure of the ____ in RBC size.

Answer 34

volume
content
concentration
variation

Question 35

Disorders of Red Blood Cells

Anemia – Risk assessment
• Obtain a careful ____ to identify conditions associated with anemia.
• The assessment should include questions concerning dietary ____, malnutrition, alcohol or drug use, use of ____ drugs, menstrual blood loss, pregnancies, ____, jaundice, gallstones, splenectomy, bleeding disorders and abnormal Hb, and organ transplantation

Answer 35

history
intake
NSAIDs
hypothyroidism

Question 36

Disorders of Red Blood Cells

Anemia – Risk assessment
• Patients with anemia, particularly ____, may have a serious underlying disease such as ____, GI bleed, or carcinoma, for which early detection may be lifesaving.
• An undiagnosed patient with classic signs or symptoms of anemia should be referred to a ____ and screened by appropriate laboratory tests.
• The severity of a patient’s anemia is important for preventing complications and the patient’s underlying condition should be ____ before proceeding with routine dental treatment.

Answer 36

men
peptic ulcers
physician
stable

Question 37

Disorders of Red Blood Cells

Anemia – Risk assessment
• To minimize the risk of medical complications, Hb levels should be above ____ g/dL, and the patient should be free from ____.
• Patients who are short of ____, have an abnormal heart rate, or have an oxygen saturation less than ____ are considered medically unstable, and routine treatment should be ____.

Answer 37

11
symptoms
breath
91
deferred

Question 38

Disorders of Red Blood Cells

Iron deficiency anemia
• Depletion of iron commonly occurs with blood loss caused by ____, pregnancy, or bleeding from the gastrointestinal (GI) tract.
• Anemia in men usually indicates the presence of a serious underlying medical problem (e.g., ____ bleeding, malignancy).
• Malabsorption of iron can result from ____ or intestinal disease that reduces absorption of iron from the ____ and the jejunum.

Answer 38

menstruation
GI
gastrectomy
duodenum