Hematologic disorders Flashcards
What is erythropoiesis stimulated by?
Human RBC production (erythropoiesis) is stimulated by erythropoietin in the kidney
Where are RBCs produced?
Continuously produced in red bone marrow by committed stem cells
How long does it take for RBC formation to maturity
~7 days
How long is the lifespan of RBC?
120 days
Rate of RBC production
2 million cells/sec
What is the reticuloendothelial system (RES)?
- Spleen, liver, bone marrow
- Responsible for removing old or defective RBCs
What happens to the plasma membrane as RBC ages?
Plasma membrane undergoes changes increasing susceptibility to phagocytosis (eryptosis)
What is the rate of eryptosis equivalent to?
Rate of eryptosis = rate of erythropoiesis
Disorders of increased eryptosis
- Sepsis
- Malaria
- Sickle cell anemia
- Beta thalassemia
- Glucose-6-phosphate dehydrogenase deficiency
- Iron deficiency
- Wilson disease
What is anemia?
Anemia is reduction of RBC volume, hemoglobin concentration below range or values that occur in healthy person (12-18g/100mL)
Acquired hypoproliferative anemia
- Nutritional deficiency (iron, folate, vitamin B12 deficiency)
- Acquired aplastic (pancytopenia)
- Transient erythroblastopenia (may have viral cause)
- Anemia of acute inflammation
- Marrow replacement by malignancy (ex: leukemia)
- Effects of drugs or toxins (ex: lead poisoning)
Congenital hypoproliferative anemia
- Diamond Blackfan syndrome
- Refractory sideroblastic anemia
Congenital hemolytic anemia
- Inherited disorders of hemoglobin
- Hemoglobinopathies (sickle cell disease, alpha and beta thalassemia)
- Enzymopathies (ex: G6PD deficiency)
- RBC membrane disorder (hereditary spherocytosis)
Acquired hemolytic anemia
- Autoimmune hemolysis – body makes antibodies against own RBCs
- Autoimmune disorders
- Systemic lupus (SLE) rheumatoid arthritis, ulcerative colitis
- Hemolysis related to infection
- (CMV, Epstein Barr Virus, hepatitis) Rh/ABO incompatibilities
What possible hematological abnormality may be associated w/ oral ulcers?
Neutropenia
What possible hematological abnormality may be associated w/ glossitis?
- Megaloblastic anemia
- Iron deficiency anemia
What possible hematological abnormality may be associated w/ angular stomatitis?
Iron deficiency anemia
What possible hematological abnormality may be associated w/ candida?
Immunosuppression
What possible hematological abnormality may be associated w/ skin pallor?
Any anemia
What possible hematological abnormality may be associated w/ jaundice?
Hemolytic anemia
What possible hematological abnormality may be associated w/ excessive bruising?
- Coagulation disorder
- Thrombocytopenia
What possible hematological abnormality may be associated w/ purpuric/petechial rash?
Thrombocytopenia
Dental considerations for a low risk anemic patient
Cause of anemia known, cause corrected, normal hematocrit, on therapy, asymptomatic: treat as normal
Dental considerations for a high risk anemic patient
- Receiving repeated transfusions to prevent symptoms, abnormal pre-op screening hemogram, h/o ongoing hemorrhage, bleeding disorder + anemia:
- Hematology consult – may require RBC transfusion
- Defer elective tx until medical status is optimal
- Tx goals aimed at minimizing stress
- Deep sedation , GA + invasive surgical procedures may require hospitalization
What is sickle cell disease characterized by?
Hemolysis, chronic organ damage, acute complication
What causes sickle cell disease?
Variant of the beta globin gene causing the sickling of RBC
Systemic manifestation of sickle cell disease
- Predisposition to infections
- Splenic sequestration (Hb levels <6 g/dL)
- Acute vaso-occlusive pain
- Avascular necrosis
- Neurologic complications/stroke
- Pulmonary disease (acute chest syndrome)
- Renal disease
- CV disorders (cardiomegaly or murmurs)
Dental manifestation of sickle cell disease
- Pale/jaundiced mucosa
- Increased susceptibility to infection
- Delayed eruption of permanent dentition
- Step-ladder trabeculation pattern
Sickle cell disease tx
- Hydroxyurea (increases level of HbF)
- Hematopoietic stem cell transplant
- RBC transfusion
Dental considerations for patients w/ sickle cell disease
- Obtain detailed patient hx
- Prescribe abx + pain medicine when appropriate to avoid crisis
- No contraindications for LA w/ vasoconstrictor
- Avoid hypoxia when using N2O or sedative agents
- Monitor patients routinely for osteomyelitis
- Risk of complications based on: type of sx planned, recent disease activity, h/o organ dysfunction, age, genetic haplotype
Dental considerations for low risk SCD patients
Dental restorations + simple extractions can be performed on an outpatient
Dental considerations for moderate + high risk patients
- May require pre-sx + post-sx admission
- Patient may need blood transfusion prior to sx
Hemophilia A
Factor VIII deficiency
Hemophilia B
Factor IX deficiency
Von Willebrand disease
vW factor deficiency
Hemophilia w/ inhibitor
- Patients may develop an antibody to factor replacement routinely given prophylactically
- Dental tx: No mandibular block injections
- In younger children, this may be indication for dental rehab under GA to get all tx completed at once (usually oral intubation)
Hereditary thrombophilia: Protein C, S, and Factor V Leiden
Increased tendency to form clots in veins
Acquired clotting factor deficiencies
- Hepatic disease - deficiency of proteins C and S
- Malabsorption problems
- Heparin therapy
- Drug induced
- Vitamin K deficiency → hypoprothrombinemia
- Affects factors II, VII, IX, X
How are platelets produced?
Via pluripotent stem cells in bone marrow
What is the life cycle of platelets regulated by?
Thrombopoietin (produced by kidney + liver)
How long does the entire process of platelets take?
~10 days
New platelets are stored in the spleen** for up to **3 days
What is the life span of a platelet?
7-10 days
What % of platelets are in circulation? Where are the remaining stored?
~60-75% of platelets are in circulation
Remainder are housed in the spleen
What do platelets have membrane receptors for?
- Collagen
- ADP
- Von Willebrand Factor
- Fibrinogen
- Thrombopoietin
- Thrombin
- Clotting factors: VIII, IX, Xa, XI
Clotting cascade
Platelet disorders – thrombocytopenia
- Bone marrow failure
- Aplastic anemia
- Leukemia
- Metastatic cancer
- Folate deficiency
- Vitamin B12 deficiency
- Drug induced
Peripheral platelet destruction – immune-mediate
- ITP (immune thrombocytopenic purpura)
- Post-transfusion
- Drug induced
- Furosemide
- Gold
- NSAIDs
- PCN
- Quinidine
- Sulfonamides
- Heparin
Platelet destruction – non-immune mediated
- TPP
- Hemolytic uremic syndrome
- Disseminated intra-vascular coagulation
- Chemotherapy
- Valproic acid (depakote for seizures)
Abnormal distribution/hypersplenism
- Partial HTN
- Inflammatory disease
- Cancer
Drug-induced platelet dysfunction
- Aspirin
- Irreversible disruption of COX-1
- Blocks ability of platelets to aggregate
- Normal platelet function returns when affected platelets are replaced
- Ibuprofen
- Reversible inhibition of COX-1
- Platelet function usually returns in 24 hrs
- Co-administration of ibuprofen w/ aspirin may diminish aspirin’s effects
- Naprosyn
Congenital platelet dysfunction
- Von Willebrand disease
- Hereditary hemorrhagic telangiectasia (characterized by multiple small AVMs)
- Management may include laser, iron supplements, or embolization
- Glanzmann’s thrombastenia (failure of aggregation)
Acquired platelet dysfunction
- Henoch Schonlein Purpura (characterized by itchy purpuric rash)
- Typically follows an infection
- Spontaneous remission
- Vasculitis of SLE
- Chronic renal failures
Disorders of connective tissue matrix of blood vessels
- Marfan syndrome
- Ehlers-Danlos syndrome
- Scurvy (arr!)
Dental considerations for platelet disorders
- Health Hx
- Frequent nosebleeds
- Heavy menstrual cycles
- Easy bruising
- family h/o bleeding disorders
- h/o excessive bleeding following sx
- Physical findings
- Petechiae
- Ecchymosis
- Generalized spontaneous gingival bleeding
- Lab screening
- Prothrombin time (PT) may be elevated due to warfarin, liver disease, vitamin K deficiency
- Partial thromboplastic time (PTT) may be prolonged due to heparin, vW disease, liver disease
- Platelet count
- INR
- Hematology consult: Mandatory in presence of significant historical, physical or lab findings
Prothrombin time (PT)
Measures extrinsic clotting system + common pathway
Partial thromboplastic time (PTT)
Measures intrinsic clotting system + common path
INR - international normalized ratio
- Based on a mathematical conversion of the PT to account for differences in lab assays
- Normal INR = 1.0
- Patients on Coumadin, targeted INR = 2-3
