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gingival bleeding-bleeding in gums that indicate some systemic disorder

fatiguability-condition where person tired or exhausted with minimal phy or mental exertion

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1. 20-year-old male

2. gingival bleeding of one day duration episodes of nose bleed

3. fatiguability, headaches

4. no significant past medical or surgical history

5. neither  smokes nor drinks alcohol

6. not taking any regular medication.

7. No history of allergy to drugs reported.

8. Family and social history  were unremarkable.

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1. pale

2. multiple  ecchymotic skin lesion measuring from 2 to 3 cm in diameter on  lower extremities.

3. Pulse rate, high, sinus rhythm

4. presence of abnormal mononuclear showing Auer  rods in the cytoplasm with few typical Faggot cells.

5. diagnosis of acute myeloid leukaemia  (AML).

With the finding of bleeding manifestations associated with

6. abnormal blood coagulation tests accompanied by progressive  thrombocytopenia, decreasing fibrinogen, and elevated D-Dimer  levels, the patient was diagnosed as having laboratory

7. evidence  of disseminated intravascular coagulation (DIC).

8. Hemoglobin (g/L) 79 | 135-175

9. Hematocrit (l/l) 0.33 | 0.40-0.52

10. MCV, MCH, MCHC, RDW normal

11. Neutrophil low

12. Lymphocytes low

13. Abnormal mononuclear cells high

14. Platelet count low

15. C-Reactive Protein high

16. D-Dimer assay high

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1. 20-year-old male -young adult,immune response in optimum,weaker compared to female ,prone to get lymphoma

2. gingival bleeding of one day duration episodes of nose bleed- continuous indicated insufficient amount of platelet (thrombocytopenia), potential anaemia:

aplastic anemia ,MDS

cause of bleeding: (can be spontaneous or not)

trauma

bone marrow disorder

nutrient deficiency

genetic disorder

infections

gum hygiene(inflammation)

dengue (haemorrhagic fever)

mechanism of bleeding

MAHA

AML-DIC

homeostasis of coagulant defect,rupture of blood vessel (over sneezing)

platelet defect,the quality

coagulation defect

3. fatiguability, headaches

anaemia

hypoxia

bone marrow suppresant

dehydration

heat stroke

4. no significant past medical or surgical history

no comorbidities

no organ transplant

immunocompetent

5. neither  smokes nor drinks alcohol

no oral cancer (less possible)

healthy person

ruled out thrombocytopenia-abuse alcohol

no exposed to chemicals,carcinogens,no tobacco

6. not taking any regular medication

bleeding not associated with drugs

7.No history of allergy to drugs reported

not related to allergy reaction

8. Family and social history  were unremarkable

coagulation cascade

pathological of bleeding (hemorrhage)

abnormal vascular permebility

could be trauma

clotting fac deficiency

ruled out medication

thrombocytopenia

iron deficiency-impairement collagen formation

G6PD

vitamin C /K deficiency

anticoagulant

possible diagnosis

MDS

aplastic anaemia

acute leukimia

scurvy

viral infection (haemorrhage)

MM,MULTIPLE MYELOMA

AML-APML-DIC

trauma

coagulopathy

further investigation

vital sign

phy exam

fbc

fbp

bone marrow aspiration

immunophenotyping

cytogenetic

molecular studies

blood coagulation test

viral serology

D-dimer (detect DIC)

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ecchymotic skin lesion- skin that turn discolour due to a bruise (blue, purple brown black, yellow)

organomegaly- enlargement of organ often detected during physical examination

lower extremities- lower part of body (limb)

cytochemistry study- lab technique to detect chemical composition of cell

Auer  rods- large, crystalline inclusion in cells that are a hallmark of APML

Faggot cell-blast with multiple Auer rods, indicates APML

abnormal mononuclear- mononuclear cells which are lymphocytes, monocytes that appear abnormal

DIC- a condition where blood clots forms through out the body leading to bleeding and organ damage

D-Dimer- protein fragments indicates blood clotting problem, fibrin degradation

International normalized ratio (INR)- blood test measure how long the blood to clot

Activated partial thromboplastic time- blood test that measure the time for blood clot

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1. pale

correlate low hb

low oxygen transport

anaemia

cause by bone marrow infiltration and impaired erythropoiesis (due to leukemia)

2. multiple  ecchymotic skin lesion measuring from 2 to 3 cm in diameter on  lower extremities.

vessel injuries, rupture

bleeding disorders

1. Pulse rate, high, sinus rhythm

tachycardia

body mechanism due to low hb

1. presence of abnormal mononuclear showing Auer  rods in the cytoplasm with few typical Faggot cells.

hallmark for APML

5. diagnosis of acute myeloid leukaemia  (AML).

APML

Correlates w DIC

genetic disorder- t(15;17)

PML-RARa- function as transcription reppressor

arrest differentiation of abnormal promyelocytes

6. abnormal blood coagulation tests accompanied by progressive  thrombocytopenia, decreasing fibrinogen, and elevated D-Dimer  levels, the patient was diagnosed as having laboratory

disturbance of coagulation

by granules of leukemic promyelocytes

causes bleeding

blood clotting problems due to platelet consumed in ongoing clotting process

7. evidence  of disseminated intravascular coagulation (DIC).

substance release from the granules of the leukemic promyelocytes

disturbance of coagulation

cause bleeding

also due to defect in homeostatis (anti and pro coagulant)

hypercoagulation and bleeding tendency

coagulation cascades:

nak create fibrin mesh

convert protrombin to trombin

trombin convert fibrinogen to fibrin (monomers)

bila fibrin banyak, dia bind (polymerised) ke fibrinogens- become fibrin-fibrinogen complex

causes:

platelet depletion

clotting factor low

fibrinolysis high

overconsumption of platelet

normal cascade coagulation:

thrombin

plasmin

fibrinogen

fibrin

plasminogen- activated to plasmin, digest fibrin, dissolve clotting

fibrinolysis- dissolve the clotting

8. Hemoglobin extremely low

severe anaemia

supress bone marrow activity

less oxygen transport

9. Hematocrit low

anaemia

sama atas

10. MCV, MCH, MCHC, RDW normal

normochromic normocytic anaemia

11. Neutrophil low

neutropenia

bone marrow suppression

transcriptional repressor by PML-RARa

cause abnormal retinoic metabolism

treatment w retinoic acid

increase risk of infection

impaired diffrentiation of myeloid cells

12. Lymphocytes low

lymphocytopenia

sama atas

13. Abnormal mononuclear cells high

due to Auer rods

immature red cells (myeloblast)

14. Platelet count low

thrombocytopenia

bone marrow suppression

DIC

bleeding

15. C-Reactive Protein high

indicates infection and inflammation

associated w tissue injuries and malignancy during APML

body response to cancer

cytokine release

monitor severity of inflammation

16. D-Dimer assay high

DIC

marker of fibrin degradation

signal blood clots be broken down

FURTHER INVESTIGATION

immunophenotyping

cytogenetic study

molecular studies

DIAGNOSIS

APML

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FISH- laboratory test that analyse person DNA to detect genetic changes

Complete remission- The disspearence of all signs of cancer in response to treatment but not always mean the cancer has been cured

ATRA- induce differentiate and mature the promyelocytes into wbc. Reduce risk of DIC

Chromosomal translocation- rearrangement of chromosome that occurs when genetic material is exchange between two or more chromosome

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1) Finding of the typical chromosomal translocation  t(15;17) using karyotyping, and typical immunophenotyping results  using flow cytometry study on peripheral blood cells, the patient was  diagnosed with acute promyelocytic leukaemia (APL) (WHO  classification on AML).

2) Prompt treatment of the DIC-related bleeding with blood component  therapy was initiated and led to normalisation of the blood  coagulation tests.

3) Treatment with specific combination  chemotherapy (all trans-retinoic acid (ATRA), idarubicin, and  arsenic trioxide) along with

4) Supportive care were started.

5)achieved complete remission and had a favorable response.

# data[].attributes.body
1) Finding of the typical chromosomal translocation  t(15;17) using karyotyping, and typical immunophenotyping results  using flow cytometry study on peripheral blood cells, the patient was  diagnosed with acute promyelocytic leukaemia (APL) (WHO classification on AML).

FAB AML M3

immunophenotyping- helps identify specific type of leukemia by examining the types of markers present

karyotyping- identify specific mutation influence the choice of therapy. diagnostic and prognostic value.

t(15;17) 15- PML, 17-RARa - sensitive ATRA. Transcription repressor (blocks differentiate)

FISH- Confirm the chromosomal translocation by fluorescent labelled genetic probes

2) Prompt treatment of the DIC-related bleeding with blood component  therapy was initiated and led to normalisation of the blood coagulation tests.

FFP(4 unit), platlet(4 unit), cryoprecipitates(6 unit)

3) Treatment with specific combination  chemotherapy (all trans-retinoic acid (ATRA), idarubicin, and arsenic trioxide)

induction- chemotherapy(CAR-T) and ATRA , MYELOID GROWTH FACTORS

consolidation- chemotherapy and supportive drug

ATRA- no BM supression, bind to RARA-PML fusion protein(disrupt co-repressors- allows myeloid cell differentiate). Can also improved coagulopathy(DIC)

idarubicin- a chemotherapy that interferes with the DNA replication and repair inside the cancer cells which prevents growth

arsenic trioxide(ATO)- induce apoptosis by degrade PML-RARA FUISON . Free radical

Typically combine with ATRA as treatment

The power of drugs combination

4) Supportive care were started.

PALLIATIVE care- provide relieve from pain and other symptoms.

Psychosocial support- relieve spiritually and emotionally- Kaunseling

5)achieved complete remission and had a favorable response.

PT HAS NO EVIDENCE OF SYMPTOMS AND NORMAL LEVELS OF BLOOD CELLS(MOLECULAR REMISSION)

BUT HAS A CHANCE TO RELAPSE

CONCLUSION

APL with DIC <3

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Trigger 1

A 20-year-old male presented to the emergency department  complaining of gingival bleeding of one day duration. After being  admitted to the hospital and on further questioning, the patient  informed the physician that he had been experiencing easy  fatiguability, headaches and few episodes of nose bleed. He has  had no significant past medical or surgical history. He neither  smokes nor drinks alcohol and is not taking any regular medication.  No history of allergy to drugs reported. Family and social history  were unremarkable.

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On physical examination, the patient looked pale with multiple  ecchymotic skin lesion measuring from 2 to 3 cm in diameter on  lower extremities. His lungs were clear and no organomegaly  found on abdominal examination. There was no evidence of  regional lymphadenopathy. Other systemic examination was  unremarkable.

Vital signs |Patient result |Reference value

Temperature (°C) 37.4| 36.4 – 37.6

Pulse rate (Beat per minute) 115,sinus rhythm|  60 – 100

Blood pressure (mm Hg) 110/70 |120/80

The morphology examination and cytochemistry study of the  stained smears of the peripheral blood and bone marrow aspirate  revealed the presence of abnormal mononuclear showing Auer  rods in the cytoplasm with few typical Faggot cells. These findings

were consistent with the diagnosis of acute myeloid leukaemia  (AML).

With the finding of bleeding manifestations associated with  abnormal blood coagulation tests accompanied by progressive  thrombocytopenia, decreasing fibrinogen, and elevated D-Dimer  levels, the patient was diagnosed as having laboratory evidence  of disseminated intravascular coagulation (DIC).

Laboratory results:

Parameters |Patient result |Reference value

Hemoglobin (g/L) 79 | 135-175

Hematocrit (l/l) 0.33 | 0.40-0.52

MCV (fl) 90 | 80-95

MCH (pg) 30 | 27-34

MCHC (g/L) 239 | 200-350

RDW (%) 14 | 11.5 – 16.0

Total White Cell Count (TWBC) (x 10⁹/L) 10 | 4-10

Differential WBCs count Percentage  (%)

Neutrophil 10| 40-80

Lymphocytes 5| 20-40

Monocytes 3 |2-10

Eosinophils 2 | 1-6

Basophils 0 | 0-1

abnormal mononuclear cells 80 | 00

Absolute  count (x 10⁹/L)

Neutrophil 1  | 2.5-7.5

Lymphocytes 0.5 | 1.5-3.5

Monocytes 0.3  | 0.2-0.8

Eosinophils 0.2 |  0.1-2.0

Basophils 0.0 |  0-1.0

Platelet count (x 10⁹/L)  15  | 150-400

Parameters | Patient result |Reference value

C-Reactive Protein (mg /L) 15 | < 10

Prothrombin time (seconds)  25 |  12.4 (10.8– 13.9)

International normalized ratio (INR) 1.7|  0.89 (0.64– 1.17)

Activated partial thromboplastic time (seconds)  60 | 33.5 (26.6– 40.3)

Plasma fibrinogen (g/L)  1.3|  2.78 (1.56– 4.00)

D-Dimer assay (mcg/mL)  1.8|  < 0.4

Blood urea serum electrolytes (BUSE),  creatinine, and liver function tests : Normal

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Based on the finding of the typical chromosomal translocation  t(11;17) using karyotyping, and typical immunophenotyping results  using flow cytometry study on peripheral blood cells, the patient was  diagnosed with acute promyelocytic leukaemia (APL), (WHO  classification on AML). The results of fluorescence in situ  hybridization (FISH) for the fusion gene was consistent with the  diagnosis of acute promyelocytic leukemia (APL).

The patient was transferred to the haematology-oncology unit where  prompt treatment of the DIC-related bleeding with blood component  therapy was initiated and led to normalisation of the blood  coagulation tests. Treatment with specific combination  chemotherapy (all trans-retinoic acid (ATRA), idarubicin, and  arsenic trioxide) along with supportive care were started. He  achieved complete remission and had a favorable response.

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Learning outcomes:

1. Describe the normal coagulation and fibrinolytic  systems (CHOPPA)

2. Describe the types of bleeding manifestations based on  the type of haemostasis defects. (FARZ)

3. Describe the mechanism of acute leukaemia. (CARMILLA)

4. Describe clinical features of acute leukaemia. (NABILAH)

5. Outline the WHO classification of acute leukaemia, APL  variant, and describe the role of chromosomal  translocation in the development of APL. (WAFI)

6. Describe the mechanism, clinical features, and  investigations for the diagnosis of disseminated  intravascular coagulation (DIC) in APL. (SOMES)

7. Describe the peripheral blood and bone marrow findings  in APL. (HAIKAL)

8. Describe the types and role of the cytochemistry study  in the diagnosis of AML. (AIDIL)

9. Describe the principles and outline the clinical  usefulness of karyotyping, fluorescence in situ  hybridization (FISH) and immunophenotyping in the  diagnosis of APL.  (SHAZ)

10.Describe the blood component therapy and outline the  combination chemotherapy (All trans-retinoic acid  (ATRA)) in APL. (SYAKIRA)

11. Describe the pathogenesis, mechanism and diagnosis of DIC (SINEESH)