CH13- Hematologic Disorders (non-neoplastic) Flashcards
Most common head and neck site for lymphoid hyperplasia
anterior cervical chain
Most common locations for lymphoid hyperplasia in the oral cavity
oropharynx, soft palate, lateral tongue and floor of mouth
A deep nodule of intraoral lymphoid hyperplasia appears pink, versus a superficial lesion may appear ___________
yellow-orange
Enlarged, rubbery-firm, nontender, freely moveable lymph node most likely represents
chronic inflammation –> lymphoid hyperplasia
R/o lymphoma by clinical hx (not rapidly enlarging)
What condition can cause multiple chronically enlarged non-tender lymph nodes
HIV
Histology of lymphoid hyperplasia
Differential based on histo?
sheets of well-diff lymphocytes with germinal center formation
*differential may include follicular lymphoma
Hallmark feature of hemophilia (of all kinds)
increased coagulation time
3 most commonly encountered bleeding disorders
Hemophilia A, Hemophilia B, von Willebrand disease
Most common inherited bleeding disorder
Von willebrand disease
Another name for hemophilia A
classic Hemophilia
Prevalence of:
Hemophilia A
Hemophilia B
Von willebrand disease
A: 1:10,000 person, 1:5000 males
B: 1:60,000 persons, 1:30,000 males
VWD: 1:800-1000 people
% of cases of Hemophilia A that represent new mutations
30%
Mutations in what causes hemophilia A?
Factor 8- over 900 different mutations
Patients with ?% normal F8 can live relatively normally while those with ?% bruise with even minor trauma
25%
<5%
(Hemophilia A)
Definition: deep hemorrhage resulting in a tumor like mass (can occur intraorally)
Pseudotumor of hemophilia
Deep hemorrhage of muscle, soft tissue and the joints may occur in
Hemophilia
joints= hemarthrosis
What disease accounts for 80-85% of bleeding disorders related to a specific clotting factor
Hemophilia A
Inheritance pattern for:
Hemophilia A
Hemophilia B
Von willebrand disease
X linked recessive
X linked recessive
Autosomal: rec or dom
What lab value is abnormal in Hemophilia A & B
PTT
Abnormal lab values for VWD
Abnormal PFA(platelet function assay), abnormal PTT
What is the function of von willebrand factor
glycoprotein in the plasma that helps platelets adhere to a bleeding site, also a transport molecule for Factor 8 in the plasma
Hemophilia A:
>____% of factor 8 = probable normal function
_____% Factor 8 may be mild disease
> 25%
5-40%= no treatment for normal activity, maybe treatment for surgery
<1%-need injections of clotting factors as soon as hemorrhagic event occurs to prevent crippling deformities
AVOID ___ containing medications in hemophilia and VWD
aspirin
Antifibrinolytic agent given before and after surgery in hemophilia and VWD
EACA- epsilon-aminocaproic acid
give 1 day before and 7-10 days after
What drug causes release of bound factor 8. This is given to hemophilia patients with ____% F8
desmopressin (DDAVP)
> 5% factor 8
DDAVP is used in the treatment of
Hemophilia A (>5% F8 available) VWD type 1(most common type 70-80%)
Pre purification ___% hemophiliacs infected with HIV, ___% hepatitis C
80-90
40
What percent of hemophilia A patients develop autoantibodies to Factor 8
25-30%
occurs less freq with Factor 9
Hemophilia B is also called ______, it a deficiency in ___
Christmas disease
factor 9
2 other names for plasminogen deficiency
ligneous conjunctivitis and hypoplasminogenemia
Inheritance pattern for ligneous conjunctivitis / hypoplasminogenemia
autosomal recessive
What disease is characterized by irregular fibrin deposited in plaques and nodules primarily in the mucosal surfaces
plasminogen deficiency
involvement of the eyes by plasminogen deficiency is termed
ligneous conjunctivitis= “woodlike”
Clinical appearance of plasminogen deficiency lesions
Thick creamy yellow-erythematous firm plaques and nodules
T/F plasminogen deficiency more commonly affects men
FALSE- women
Hypoplasminogenemia: Ocular lesions in ____%, oral in ___%, respiratory tract in ___%, vaginal lesions in ___%
80%
34%
16%
8%
(about half each time)
Most common site for a lesion of plasminogen deficiency in the oral cavity
gingiva-patchy ulcerated papules with irregular surface that wax and wane
The amyloid-like material seen on histology of plasminogen deficiency is negative for amyloid stains and positive for _________?
fraser-lendrum IHC
T/F patients with plasminogen deficiency are more prone to thrombus
surprisingly these patients don’t have thrombus formation problems, life expectancy is normal
treatment of oral lesions of plasminogen deficiency
- Topical heparin and prednisone combined
- Surgical excision + systemic doxy, topical chlorhexidine, systemic warfarin
Major divisions of Anemia 1. Disturbed iron metabolism 2. \_\_\_\_\_\_ anemia 3. Anemia of \_\_\_\_\_\_\_ 4. \_\_\_\_\_Anemia 5.
- Megaloblastic: Vitamin B12 def, folic acid def
- anemia of chronic disorders: infection, inflammatory CT dz, 2/2 malignancy, liver dz etc
- Hemolytic anemia: extrinsic and intrinsic
- Hemoglobin disorder aka Hemoglobinopathies: sickle cell, thalassemia
What amino acid change occurs to form Hemoglobin S
glutamic acid –> valine
Sickle cell disease
Patients with _____ have only ____% of hemoglobin affected and have sickle cell trait
1 mutated copy
40-50%
What % of the black population has sickle cell trait
8%
prevalence of sickle cell disease in blacks
1:350-400
how long are sickle cell erythrocytes in circulation
12-16 days
What are 3 most commonly affected sites in sickle cell anemia? What is acute chest syndrome?
Ischemic pain in 1. abdomen, 2. long bones and 3. lungs that occurs in sickle cell crisis…acute chest syndrome = pain in the lungs usually precipitated by a fat embolism or community aquired pneumonia
What is a common cause of death among children with sickle cell disease and thalassemia? What are the prophylaxis recommendations?
- strep pneumoniae infections
- they are more susceptible likely due to multiple splenic infarcts-
- Sickle cell: prophylactic penicillin antibiotics until age 5 and polyvalent pneumococcal vaccinations recommended
What % of children have a stroke by 8 years old as a result of sickle cell disease
5-8%
Oral findings in sickle cell disease (radiographic)
reduced trabeculation of the bone (2/2 increased hematopoiesis), increased risk osteomyelitis, infarction, asymptomatic pulpal necrosis
“HAIR ON END” radiographic appearance is described in what condition (s)? Which condition is it more prominantly seen in?
sickle cell anemia
thalassemia (more prominant)
sickle shaped RBCs are also called ____ shaped
boomerang
What is the affect of hydroxyurea? What is a curative, albeit not usually feasible treatment for sickel cell?
increases fetal hemoglobin (Hemoglobin F) in adult patients with sickle cell (inhibits polymerization of hemoglobin S and reduces adherence of RBCs to vessel walls)….CURATIVE = bone marrow transplant, but need HLA match with donor sibling - only 1% qualify
carriers of sickle cell trait and thalassemia are more resistant to _____… what is the root of the word ‘thalassemia’?
malaria…thalass = sea in Greek (Mediterranean Sea is where the first reports originated)
1 of the most common inherited conditions that affect humans…what are the two types of anemia that arise of this?
Thalassemia = 1. hypochromic 2. microcytic anemia
___ genes code for the beta chain; ____ genes code for the alpha chain of hemoglobin…how many mutations have been documented for b-thalassemia?
2 beta, 4 alpha…more than 200 different mutations
1 beta chain mutated –>
2 beta chains mutated —> ? What are the 2 alternate names?
thalassemia minor
thalassemia major aka 1. Cooley’s anemia or 2. Mediterranean anemia
Description of the type of anemia in beta thalassemia major after the patients fetal hemoglobin dissipates
Severe microcytic hypochromic anemia (occurs at 3-4 months)
Hematopoiesis to compensate in beta thalassemia major increases by _____ = massive marrow hyperplasia, hepatosplenomegaly, LAD
30x
“CHIPMUNK” face occurs in what condition and is a manifestation of what
occurs in beta thalassemia major
-painless maxilla and mandibular enlargement caused by massive marrow hyperplasia
1 deleted gene →
2 deleted genes →
3 deleted genes →
4 genes deleted (homozygous) →
1–>no detectable disease
2–>alpha thalassemia trait
Mild anemia and microcytosis. Usually not clinically significant
3–> hemoglobin H (HbH) disease. Hemolytic anemia and splenomegaly
4–>hydrops fetalis = severe generalized fetal edema
How often do thalassemia major patients need transfusions? Significant side effect from blood transfusions
every 2-3 weeks…hemochromatosis: iron overload
What medication is given to help combat hemochromatosis in thalassemia patients receiving transfusions?
deferoxamine (iron chelating agent)
Pancytopenia occurs in what condition?
aplastic anemia
failure of hematopoietic precursor cells to make all types of blood cells (cytotoxic t-cell mediated reaction)
Etiology of aplastic anemia
t cell are targeting the precursor cells in the bone marrow
Causative/inciting agents of aplastic anemia
toxins- benzene
drugs- chloramphenicol
infections- ABCG types of hepatitis
2 Genetic disorders with an increased risk of aplastic anemia
Fanconi Anemia
Dyskeratosis congenita
6 Oral changes seen in aplastic anemia
Petechiae, purpura, gingival hemorrhage
Pale oral mucosa from decreased RBCs
Oral ulcers from infections/neutropenia
Gingival hyperplasia
In a biopsy of an oral ulcer in aplastic anemia what would you see
organisms and a LACK of inflammatory response
Diagnostic criteria for aplastic anemia
based on labs: 2 or more:
- Fewer than 500 granulocytes/uL
- Fewer than 20,000 platelets/uL
- Fewer than 20,000 reticulocytes/uL
patients with aplastic anemia are at an increased risk for what malignancy
acute leukemia
Neutropenia is defined as circulating neutrophils below ______
1500/mm3
patients of African and mediterranean backgrounds can have normal neutrophil levels around 1200, this is called
benign ethnic neutropenia
Causes of neutropenia in infants are predominantly congenital or genetic such as: 1. 2. 3. 4.
- Schwachman-Diamond syndrome
- Dyskeratosis congenita
- Cartilage-hair syndrome
- Severe congenital neutropenia
6 Causes of neutropenia in adults…What is the most common type of infection to cause neutropenia?
- destruction of BM by malignancy
- destruction from metabolic diseases: Gaucher disease
- osteopetrosis
- drugs: chemo, antibiotics, phenothiazines, tranqs, diuretics
- infections: Staph aureus (or bacterial) infection = most common
- SLE
Gaucher disease
auto recessive disorder where fat-laden gaucher cells build up in spleen, liver, and bone marrow
What is a Gaucher cell
histiocytes filled with linear or fibrillar material called kerasin
Neutropenia in SLE is caused by
anti-neutrophil antibodies
Viral and bacterial infections _____ neutrophil production and ______ ______ ex. HIV, hep A&B, measles, rubella, varicella, TB, typhoid etc
reduce production anddd increase destruction
Patients with neutropenia are prone to bacterial infections, particularly ________ infection
staph aureus
Most common sites of infection in neutropenia
peri-rectal, oral cavity, middle ear
–>lung when it drops below 500 count
Oral cavity manifestation neutropenia: ulcers of the ______ that characteristically ______
gingiva; lack an erythematous border
A major treatment for neutropenia
G-CSF
granulocyte colony stimulating factor
(filgrastim, pegfilgrastim)
Agranulocytosis affects all the cell of the granulocyte lineage, but particularly _______
neutrophils
Etiology agranulocytosis
mostly drug induced
sometimes congenital
2 congenital causes of agranulocytosis (decreased level of G-CSF)
- Congenital agranulocytosis
- Kostmann syndrome (severe congenital neutropenia)
In aplastic anemia and agranulocytosis the loss of ______ is more impactful than other cell absences
neutrophils
The oral manifestation in agranulocytosis may mimic
NUG on the gingiva
Necrotizing deep punched out ulcerations
oral presentation in agranulocytosis
If drug induced _______ usually resolves within 10-14 days after the offending drug is removed
agranulocytosis
Disease course of cyclic neutropenia
- Idiopathic regular periodic reductions in the neutrophil count of affected patients
- drop lasts 3-6 days
- Uniformly spaced episodes: every ~21 days
What mutation is implicated in cyclic neutropenia? Which stage is development of the neutrophil arrested?
neutrophil elastase gene
ELA-2 aka ELANE….PROmyelocyte stage
prevalence of cyclic neutropenia? Inheritance? What is the typical length of the neutrophil cycle?
1:1 million..AD (but most cases are isolated)…every 21 days
What disease? Oral ulcers occur anywhere with minor trauma, erythematous halo is variably present. Severe periodontal bone loss and gingival recession
cyclic neutropenia
Neutrophil count falls to ____ for 3-5 days in at least 3 successive cycles for diagnosis. DX?
500
cyclic neutropenia
treatment cyclic neutropenia
G-CSF several times a week. Reduces the drop in neutrophils from 5-6 days to 1 day.
When do the symptoms of cyclic neutropenia naturally diminish
second decade of life, despite the continued cycling
What causes Thrombotic Thrombocytopenic purpura (TTP)
Deficiency in von willebrand factor cleaving metalloprotease (ADAMTS13) (or AR recessive ADAMTS13 gene mutation)
TTP: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder in which many small blood clots (thrombi) form suddenly throughout the body. it uses up all your platelets and that is why they are low.
Deficiency in von willebrand factor cleaving metalloprotease aka ADAMTS13 is caused by
autoantibodies to ADAM or inherited mutations to ADAM
ADAMTS13=a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)—also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor
Basic mechanisms of thrombocytopenia
- Decreased production
- Increased destructions
- Increased use of platelets in abnormal clotting disorders
- Platelet trapping in the spleen in splenomegaly
thrombocytopenia is usually not clinically detected until platelets are below ______
100,000
normal 200,000-400,000
Acute ITP: Immune(previously idiopathic) thrombocytopenic purpura occurs in what age group
Childhood
Acute ITP usually resolves spontaneously in _____ weeks. ___% of pts recover in 3-6 months
4-6 weeks
90%
Chronic ITP: Immune(previously idiopathic) thrombocytopenic purpura occurs in what age group
20-40 year old women
Cause of chronic ITP
Autoantibodies to platelet surface antigens leads to sequestration of the platelets in the spleen
Treated with splenectomy
What condition? 30-40% of oral biopsy show fibrin deposits in small vessels (PAS stain)
thrombocytopenia
3 Other names for: Polycythemia vera
(primary polycythemia, polycythemia rubra vera; primary acquired erythrocytosis)
Polycythemia vera is defined as
an increase in the MASS of the RBCs (also freq uncontrolled production of platelets and granulocytes too)
What is the aquired mutation in polycythemia vera?
JAK2 (janus kinase 2)
What is the peripheral vascular event assoc with polycythemia vera?
erythromelalgia
What % of polycythemia vera patients develop leukemia?
2-10%
