13 Hematologic Disorders Flashcards
-Proliferation of lymph cells in response
to an antigenic challenge n Location
-oropharynx, soft palate, lateral tongue, FOM
-Lymphadenopathy
-acute- enlarged, tender, soft, freely
movable
-chronic- enlarged, non-tender, rubbery, firm, freely moveable
-Tonsillarasymmetry
-Potentially serious sign- R/O neoplasia
Lymphoid Hyperplasia
*****Represents a variety of bleeding disorders associated with genetic deficiencies of any one of the clotting factors
Hemophilia
- hemophilia A - factor VIII deficiency, 85%
- hemophilia B - factor IX deficiency, 1/50,000
- von Willebrand’s disease - deficiency of a plasma glycoprotein; 1/800
- joints can get huge
clinical features:
- X-linked
- severity depends on extent of clotting factor deficiency
- Increased coagulation time is a hallmark feature
- Hemarthrosis (big joints)
- ASA (aspirin) strictly contraindicated
Hemophilia
-80% to 90% of hemophiliac patients treated with cryoprecipitate
- General term for a drop in the Hematocrit or Hemoglobin concentration
- Develops when not enough RBC to transport oxygen to organs or RBC deficient in hemoglobin
- often a sign of an underlying disease (blood loss, decreased production of rbcs, or increased destruction of rbcs)
anemia (iron deficient is the most common?)
- Causes:
- renal failure, liver disease, chronic inflammatory diseases, malignancies, vitamin or mineral deficiencies
what are the symptoms of anemia?
- Central: fatigue, dizzyness, pallor (mouth and palpebral conjuntiva), fainting
- Heart: palpitations, rapid heart rate, chest pain, angina, heart attack, low blood pressure
- Respiratory: SOB
- Muscular: weakness
- Skin: paleness, yellowing, coldness
- Spleen: enlargement
- Intestinal: changed stool color
In sickle cell anemia patients, they are susceptible to infection, what organism is especially associated with sickle cell?
Streptococcus pneumoniae (?)
what is sickle cell anemia, and what are the different types?
- an inherited blood disorder of blacks and those of mediterranean origin
- severe disorder of hemoglobin synthesis
- Heterozygous-sickle cell trait- asymptomatic
- homozygous-sickle cell anemia- Females
- abnormal hemoglobin causes cells to sickle in presence of low oxygen
if you seen “hair-on-end” manifestation on skull radiograph, the patient has….?
sickle cell anemia
what conditions can trigger the sickleing phenomenon of sickle cell anemia?
- exercise, exertion, administration of general anesthetic, pregnancy, sleep
- sickle cells can’t pass through small blood vessels and are destroyed more rapidly than normal
-Clinical/Oral Features
-Weakness/fatigue
-Shortness of breath
-Joint pain
-Nausea
-Loss of trabeculation with development of
large marrow spaces
-Step-ladder trabeculation
-Hair-on-end skull a
appearance
sickle cell anemia
description of hair on end appearance
- Ineffective erythropoiesis, peripheral destruction of erythrocytes or decreased oxygenation of arterial blood lead to exuberant hyperplasia of the erythroid linage in the bone marrow.
- The constant quest for more space for erythropoiesis leads to widening of the diploid space of the cranial vault, thinning of the outer table with trebecular destruction and thickening of the remaining trabeculae perpendicular to the curvature of the brain.
diagnosis and treatment of sickle cell anemia
- Diagnosis
- Blood smear reveals sickle cells
- Hematocrit and mean hemoglobin low
- Treatment
- Symptomatic and supportive
- Administration of oxygen and fluids
- Can lead to cardiac failure
1) Reduced synthesis of either alpha or beta globulin chains of the hemoglobin molecule
2) Heterozygous form – only one gene involved – thalassemia minor – asymptomatic
3) Homozygous form – more than one gene - thalassemia major (Mediterranean or Cooley’s anemia) severe hemolytic anemia due to damage to red blood cell membranes and destruction of RBCs
Thalassemia
- treated with blood transfusions
- their spleen can get huge
1) Clinical manifestations
a) T. major begins early in life – pale, listless,
infections
b) Yellow skin, pallor, fever, malaise, weakness
c) Prominent cheekbones, depressed nasal bridge, prominent premaxilla, flaring of maxillary anterior teeth
2) Oral manifestations
a)Peculiar trabecular pattern in jaws
b)Some trabeculae are prominent, others blur and disappear – “salt and pepper” appearance
c) Thinning of lamina dura
d) Circular radiolucencies in alveolar bone
e) Hair on end appearance of skull
Thalassemia
treatment for thalassemia
- Blood transfusions q2-4 weeks (4-6 hours) + nightly
- subcutaneous infusion deferoxamine 10-12 hours -Splenectomy
- These provide periods of remission but prognosis is poor – for some patients BMT is successful
1) Life threatening
2) Failure of hematopoietic precursor cells in BM to produce adequate numbers of all types of blood cells
3) Thought to be an immune-mediated disease caused by cytotoxic T lymphocytes targeting hematopoietic cells
Aplastic Anemia
1) Hematopoietic stem cells do not undergo normal maturation in spite of normal or increased levels of cytokines (such as GMCSF)
2) Underlying trigger for the immune mediated destruction unknown
3) Environmental toxins, drugs, viruses, genetic (Fanconi’s anemia and dyskeratosis congenita)
aplastic anemia
what are the clinical findings of aplastic anemia?
- Erythrocyte deficiency sign of anemia
- Platelet deficiency signs of thrombocytopenia
- Retinal and cerebral hemorrhages
- WBC deficiency (neutropenia, leukopenia and granulocytopenia) lead to bacterial and fungal infections and often cause of death
1) Decrease in the number of circulating neutrophils below 1500/mm3
2) increased susceptibility to infection
- Mechanisms
- Decreased production n Increased destruction
- Drugs- chemo, antibiotics, diuretics, etc n -Nutrition- Vit. B12 or folate deficiency
- Bacterial and viral inflections
3) S. aureus and gram-negative organisms
4) Gingival mucosa- - common site
Neutropenia
- this is a correctable disease,
- tx with G-CSF and GM-CSF(?)
- Cells of the granulocytic series are absent
- Decreased production
- Increased destruction n Idiopathic
- Drug induced
- Clinical symptoms
- Malaise, sore throat, fever, swelling chills, bone pain, pneumonia, shock
- Oral lesions are common (ulcerations and NUG)
- Treatment: Discontinue drug; G-CSF and GM-CSF
- Mortality was 20-30%; now improved with cytokines and antibiotics
Agranulocytosis
-the difference between this and neutropenia is neutropenia is only neutrophils, but this is all the granulocytes
-Rare idiopathic hematological disorder that is characterized by regular periodic reductions in the neutrophil population
-low neutrophil counts are present 3 to 6 days -usually about a 21 day cycle
-Clinical signs include:
-fever, anorexia, cervical lymphadenopathy, malaise,
pharyngitis, oral and mucosal ulcerations
-ulcers with erythematous halo
-gingiva may be severly affected
-bone loss, recession and mobility
cyclic neutropenia
-they usually have periodontal issues
1) Decreased #s of circulating blood platelets
2) Platelets necessary for hemostasis and clot formation
3) 200,000-400,000/mm3 normal
4) Decrease due to:
- Reduced production
- Increased destruction
- Sequestration in the spleen
Thrombocytopenia
Clinical features
-Not usually seen until count below
100,000 mm3 (more like below 60 K)
-Leakage of blood from small vessels producing small pinpoint hemorrhagic lesion called petechiae and larger lesions called ecchymosis
-With even larger amounts of blood a hematoma forms
-Gingival bleeding and bleeding from sites of minor trauma
thrombocytopenia
Serious disorder of coagulation caused by some form of endothelial damage that appears to trigger the formation of numerous thrombi within small blood vessels of the body
Thrombotic thrombocytopenic purpura (TTP)
treatment and prognosis of thrombocytopenia
-Discontinue drug and platelet count
returns to normal in few days
-ITP usually resolves spontaneously but some cases require CS or IVIG
-TTP relatively guarded; outlook improved since therapy with plasmapheresis or plasma exchange transfusions (70% survival with proper tx)
- Idiopathic hemorrhagic disorder thought as an increase in mass of RBCs (too many RBCs)**
- Believed to be a single progenitor marrow stem cell which begins multiplying without regard to normal regulatory hormones (erythropoietin)
- Excessive numbers of formed elements of the blood at 2x-3x normal rate
- Cells generally function normally
Polycythemia Vera
- first treatment is usually phlebotomy
- Anagredilde hydrochloirde if platelet levels need to be controlled
- antihistamines to control purities
- Represents several types of malignancies of hematopoietic stem cell derivation
- Proliferation in bone marrow with overflow into the peripheral blood
- Acute versus chronic
- Myeloid vs. lymphocytic
- Genetic + environmental
leukemia
what syndromes put you at greater risk for leukemia?
- Down
- Neurofibromatosis 1
- Klinefelter
- Fanconi’s anemia
- Chronic myeloid L and the Philadelphia chromosome (chromosome material between the long arms of 22 and 9)
- Myelodysplasia syndromes (early stages in the development of acute myeloid L)
crowding out of the normal hematopoietic stem cells by the malignant proliferation
myelophthisic anemia, some association with leukemia
- In childhood and after a nonspecific viral infection
- Symptoms occur quickly and may be severe
- Most cases resolve quietly in 4-6 weeks and 90% recover by 3-6 months
Idiopathic (immune) throbocytopenic purpura (ITP)
acute lymphoblastic leukemia
-almost always children
chronic lymphocytic leukemia
primarily affects elderly adults
what are the different types of leukemia?
1) Myeloid: generally adult population
a) acute myeloid-broad age range
b) chronic myeloid-peak in thir and fourth decades
2) lymphocytic/lymphoblastic
a) acute lymphoblastic-almost always children
b) chronic lymphocytic- primarily affects elderly adults
- Originally thought a skin disease
- T cell lymphoma
- Epidermotropism (propensity to invade epidermis)
Mycosis Fungoides
-2:1 male; mean age 55-60
-Eczematous phase often mistaken
for psoriasis;
-Plaque stage (distinct nodules and papules)
-Tumor phase
-Sezary syndrome; aggressive expression that represents a dermatopathic T-cell leukemia
Mycosis Fungoides
- not considered curable and is usually slowly progressive
- median survival 8-10 yrs
- once it progresses beyond cutaneous involvement it’s much worse and patient dies of organ failure of sepsis
-B-cell malignancy that represents an undifferentiated lymphoma -Related pathogenetically to EBV -50-70% present in the jaws -Children with peak 7 years of age -Maxilla 2:1 over mandible - Aggressive neoplasm that results in the death of the patient within 4-6 months without treatment -More than 90% respond to treatment and disease free survivals are the norm with the new protocols
Burkitt’s lymphome
- 90% of 3 year olds jaw lesion and only 25% older than 15 have jaw lesions
- Radiographic features consistent with a malignant process; patchy loss of lamina dura early sign
- Histologically “starry sky” histiocytic cells with abundant cytoplasm set in a background of malignant , darkly staining lymphoma cells.
Plasma cell malignancy that appears to have a multicentric origin within bone
- 1% of malignancies and 10-15% of hematologic malignancies
- Rarely diagnosed before 40; males >; bone pain presenting symptom; blacks 2X
- Radiographically “PUNCHED OUT***” bony lesions; jaws 30% of cases
- Renal failure may be presenting sign; kidneys overburdened with the circulating light chain products
- Light chain products found in urine Bence Jones proteins
- 15% show deposits of amyloid (A) due to abnormal light chain accumulation and this may be the initial manifestation
- Tongue may show enlargement and firmness or nodular appearance due to A
multiple myeloma
- Median survival 30-36 months with 25% five year survival
- With aggressive chemotherapy and BMT the overall 5 year survival increased to 50% and 20% over 10 years (only a small % can tolerate this therapy)
-Monoclonal gammopathy
-Confluent sheets of monoclonal
(light chain restricted) plasma cells
-Kappa or lambda light chain restricted
-Amyloid positivity with Congo red demonstrating apple-green birefringence with polarized light
multiple myeloma
Treatment and prognosis
-Median survival 30-36 months with 25% five year survival
-With aggressive chemotherapy and BMT the overall 5 year survival increased to 50% and 20% over 10 years (only a small % can tolerate this therapy)
- Unifocal, monoclonal, neoplastic proliferation of plasma cells that usually arises within bone
- Extramedullary P (90% H & N)
- Work up for MM
- Ave age 55 and 3:1 male and 6:1 extramedullary
Plasmacytoma
- Unilocular radiolucency with no evidence of a sclerotic border
- Most lesions single site and spine most common
- Treatment – radiation therapy at least 4000 cGy
- 50% disseminated disease within 2-3 years
- May develop into MM (33% no symptoms of MM for 10 years)
- Extramedullary only 30% progression to MM and 70% 10 year disease free period
plasmacytoma
determining malignancy using staining
-kappa and lambda stains
If only one is positive=malignancy, if both, probably inflammatory rxn
Prognosis of children with ALL (Leukemia)
80% cured, in adults remission is high/80% but 5 year survival lower
Patients younger than 60 with AML (leukemia) prognosis
-5 year survival of 40%, over 60 yr old=10%
Prognosis of CML (leukemia)
20% five year survival
CLL (leukemia) prognosis
incurable
- proliferation of histiocyte-type cells accompanied by eosinophils, L, PC and multinucleated giat cells
- 50% occur in children under 10
- bone lesion most common clinical presentation
- jaws affected 10-20% of cases
- teeth may appear to be floating in air
- in bone may simulate PAP
Langerhans cell Histiocytosis
- Langerhan cells are dendritic-mononuclear cells found in the epidermis, mucosa, LN, and BM
- they process and present antigens to T lymphocytes
- malignant lymphoproliferative disorder
- neoplastic cells (Reed-Sternberg cells) =1-3% of the cells in enlarged lymph nodes
- persistently enlarging, nontender mass or masses in one lymph node region
- Where are the enlarged lymph nodes usually found?
Hodgkin’s Lymphoma
- cervical and supra-clavicular nodes=75%
- axillary and mediastinal nodes=%-10%
- abdominal and lunguinal
- A diverse group of malignancies of lymphoreticular histogenesis
- usually arise in lymph nodes (20-40% extranodal)
- grow in solid masses-b-lymphocyte series 85%
- low, median and high grade
- primarily adults
- nontender slowly enlarging mass
- initially freely movable
- more numerous and fixed over time
- in bone ill defined or ragged radiolucency
- expansion of bone with cortical perforation
- oral lesions typically have a boggy consistency
Non-Hodgkin’s Lymphoma
- may appear erythematous or purplish and may or may not be ulcerated
- buccal vestible, posterior hard palate and gingiva
which disease, when in bone, may be mistaken for a toothache?
-numb chin syndrome due to paresthesia in mandibular lesions
Non-Hodgkin’s Lymphoma
1- Radiation and/or chemotherapy
a- Low grade – slow growing, tend to recur despite therapy (some feel “watch and wait”), older adults, median survival with treatment is 10 years (40% eventually transform to high grade)
b- Intermediate grade (IG) – 30-50% failure rate
c- High grade (HG) – 60% mortality rate after diagnosis
d-Response rate in IG and HG is good but the cure rate is not high
- Bence Jones proteins in Urine
- Punched out bony lesions
Multiple Myeloma
